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THE BREAST
Editor-in-Chief
Fatima Cardoso, Champalimaud Cancer Centre, Lisbon, Portugal
Co-Editors
Alberto Costa, Canton Ticino Breast Unit, Lugano, Switzerland
Nehmat Houssami, University of Sydney, Sydney, Australia
Specialty Editor
Epidemiology and prevention
Surgery and gynaecology
Imaging, screening and early diagnosis
Medical oncology and translational medicine
Pathology
Psycho-oncology
Radiation Oncology
Nursing and Quality of Life
Advocacy
Translational Research
Australasian Society for Breast Disease Representative
EUSOMA – European Society of Breast
Cancer Specialists Representative
St Gallen Conferences Representatives
Breast Centres Network Representative
E. Negri, Milan, Italy
M.J. Cardoso, Lisbon, Portugal
A. Rody, Luebeck, Germany
N. Houssami, Sydney, Australia
E. Senkus-Konefka, Gdansk, Poland
P. Francis, Melbourne, Australia
G. Pruneri, Milan, Italy
L. Travado, Lisbon, Portugal
P. Poortmans, Nijmegen, The Netherlands
Y. Wengström, Stockholm, Sweden
S. Knox, Milan, Italy
S. Di Cosimo, Milan, Italy
R. Stuart-Harris Canberra, Australia
J. Harvey Perth, Australia
C. Markopoulos Athens, Greece
B. Thürlimann St Gallen, Switzerland
H.J. Senn St Gallen, Switzerland
C. Tinterri Milan, Italy
International Advisory Board
Chairs: Monica Morrow New York, USA
B. Anderson Seattle, USA
J. Apffelstaedt Tygerberg, South Africa
R.A. Badwe Mumbai, India
G. de Bock Groningen, The Netherlands
J. Bogaert Brussels, Belgium
H. Bonnefoi Bordeaux, France
M. Brennan Sydney, Australia
G. de Castro Sao Paulo, Brazil
R.E. Coleman Sheffield, UK
T. Cufer Slovenia
S. Delalogue Villejuif, France
J. M. Dixon Edinburgh, Scotland
S. Duffy London, UK
L.E.M. Duijm Nijmegen, Netherlands
N. El Saghir Beirut, Lebanon
J. Garber Boston, USA
W. Gatzemeier Milan, Italy
Hirotaka Iwase Kumamoto, Japan
J.Gligorov Paris, France
I.C. Henderson San Antonio, USA
A. Howell Manchester, UK
B. Kaufman Ramat Gan, Israel
M. Kaufmann Frankfurt, Germany
N. Kearney Stirling, UK
H. de Koning Eindhoven,
The Netherlands
S. Kyriakides Nicosia, Cyprus
F. Levi Lausanne, Switzerland
L. Lusa Ljubljana, Slovenia
S. Michiels Brussels, Belgium
S. Ohno Fukuoka, Japan
M. Paesmans Belgium
O. Pagani Lugano, Switzerland
X. Paoletti Paris, France
G. Pond Hamilton, Canada
K. Pritchard Toronto, Canada
C. Rageth Zurich, Switzerland
M. Roselli Del Turco Florence, Italy
I. Rubio Barcelona, Spain
V. Sacchini New York, NY, USA
K. Sandelin Stockholm, Sweden
F. Sardanelli Milan, Italy
G. Schwartsmann Porto Alegre, Brazil
V. Semiglazov St. Petersburg, Russia
L. Solin Philadelphia, USA
E. Tagliabue Milan, Italy
U. Veronesi Milan, Italy
D.A. Vorobiof Johannesburg, S.A.
M.G. Wallis Cambridge, UK
A. Wardley Manchester, UK
N. Williams London, UK
Y. Yarden Israel
S. Zackrisson Malmö, Sweden
J. Žgajnar Ljubljana, Slovenia
www.elsevier.com/brst
An Associate Journal of the Australasian Society for Breast Disease: www.asbd.org.au
Affiliated with the European Society of Breast Cancer Specialists: www.eusoma.org
Official Journal of Breast Centres Network: www.BreastCentresNetwork.org
Amsterdam • Boston • London • New York • Oxford • Paris • Philadelphia •
San Diego • St Louis
VOLUME 24 SUPPLEMENT 3
November 2015
Advanced Breast Cancer Third International Consensus Conference - Abstract Book
Welcome
General Information
High Patronage
Endorsement and Auspices
Sponsors
Award
Chairs and Panel Members
Breast Cancer Patient Advocacy Programme
Programme
Sponsored satellite symposia
Abstract Presenters
Poster Session
Invited Abstracts
Abstracts – Nursing and Advocacy
Abstracts - Clinical Issues: Medical Oncology
Abstracts – Clinical Issues: Radiation Oncology
Abstracts – Clinical Issues: Surgical Oncology
Abstracts – Clinical Issues: Supportive and Palliative Care
Abstracts – Clinical Issues: Other Topics
Abstracts – Basic and Translational Research
Disclosure of Conflict of Interest
Authors Index
Abstract List
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S57
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S82
Guide for Authors
Submission to The Breast proceeds totally online via the Elsevier Editorial System page of this journal at http://ees.elsevier.com/thebreast/.
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Indexed/abstracted in: Index Medicus, MEDLINE, ABI/Inform, Current Awareness in Biological Sciences,
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National Library of Medicine (MEDLARS and MEDLINE), Research Alert, SCISEARCH, Science Citation Index, Scopus
Amsterdam • Boston • London • New York • Oxford •
Paris • Philadelphia • San Diego • St Louis
Aims and Scope
The Breast is an international, multidisciplinary journal for clinicians, which focuses on translational and clinical research for the advancement of breast cancer prevention and therapy.
The Editors welcome the submission of original research articles, systematic reviews, viewpoint and debate articles and correspondence on all areas of pre-malignant and malignant breast
disease, including:
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•
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Surgery
Medical oncology and translational medicine
Radiation oncology
Breast endocrinology
Epidemiology and prevention
Gynecology
Imaging, screening and early diagnosis
Pathology
Psycho-oncology and quality of life
Advocacy
Supportive and palliative care
Nursing
Research and management in countries with limited resources
The Breast is a valuable source of information for surgeons, medical oncologists, gynecologists, radiation oncologists, endocrinologists, epidemiologists, radiologists, pathologists, breast care nurses,
breast cancer advocates, psychologists and all those with a special interest in breast cancer.
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The Breast 24 S3 (2015) S1
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Welcome
Dear Colleagues,
The International Consensus Conference for Advanced Breast
Cancer (ABC) has established itself as a major international
breast cancer conference. Its primary aim is the development
of international consensus guidelines for the management of
ABC patients. These guidelines are based on the most up-to-date
evidence and can be used to guide treatment decision making in
many different health care settings globally, with the necessary
adaptations due to different access to care.
The last meeting, which took place in Lisbon, Portugal in
November 2013, brought together over 1000 participants from
71 countries around the world, including health professionals,
patient advocates and journalists.
ABC Consensus Conferences have the ambitious goal of
improving outcomes for all patients with advanced breast cancer.
We believe that health professionals working closely together
with patient advocates and with the strong support of media
can raise awareness about the needs and challenges faced by this
traditionally underserved and forgotten group of patients. We
aim to identify research priorities based on the most important
areas of unmet need, analyse and discuss available data to
provide the most accurate management recommendations,
but also to influence policy makers and funding bodies and
ultimately improve standards of care, survival and quality of
life. Research and education, with accurate usage of available
knowledge, throughout the world, are key to achieve these goals.
ABC guidelines are jointly developed by ESO (European School
of Oncology) and ESMO (European Society of Medical Oncology)
and guidelines or ABC conferences have been endorsed and
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
supported by several other international oncology organizations
such as ESGO (European Society of Gynaecological Oncology),
EUSOMA (European Society of Breast Cancer Specialists),
ESTRO (European Society for Radiotherapy and Oncology),
UICC (Union International Contre le Cancer), SIS (Senologic
International Society)/ISS (International School of Senology),
FLAM (Federacion Latino-Americana de Mastologia), OECI
(Organization of European Cancer Institutes), Susan G. Komen®
and BCRF (Breast Cancer Research Foundation). Furthermore, the
ABC3 faculty includes official representatives appointed by ASCO
(American Society of Clinical Oncology).
It is therefore with great enthusiasm that we welcome
you to attend the Advanced Breast Cancer Third International
Consensus Conference (ABC3).
We strongly believe that together we will dramatically change
the poor outcome of this disease and improve both the quality
and length of life of all patients living with ABC worldwide.
Through our dedicated efforts over this last decade, we can
certainly say to every ABC patient "You are no longer forgotten,
but you are still our heroes!" [1].
Fatima Cardoso, Eric P. Winer, Larry Norton and Alberto Costa
Conference Chairs
[1] *Metastatic breast cancer patients: The forgotten heroes!
The Breast 2009;18:271–272.
The Breast 24 S3 (2015) S2–S3
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
General Information
Venue
ABC3 will be held at the CCL - Centro de Congressos de Lisboa,
Praça das Industrias, Lisbon, Portugal.
Official Carrier
ESO is grateful to Star
Alliance™ members airlines
who supported the conference as Official Carrier and offered
discounted fares to our participants.
Acknowledgements
A BC 3
1 European School of Oncology, Via Turati, 29
20121 Milano, Italy.
ph +39 02 85464 532
fx +39 02 85464 545
www.abc-lisbon.org
www.eso.net
2 European School of Oncology, Piazza Indipendenza 2, 6500 Bellinzona, Switzerland
ph +41 91 820 0950
fx +41 91 820 0953
www.abc-lisbon.org
www.eso.net
3 Viagens Abreu SA, Av. 25 de Abril, 2
2799-556 Linda-a-Velha, Portugal
ph +351 21 415 6120
fx +351 21 415 6383
No smoking policy
ABC3 is a tobacco-free event. All participants are kindly asked
to respect the no-smoking policy.
ESO wishes to express its appreciation and gratitude to
the ABC3 Chairs for their support and vision in establishing
this conference, all faculty members and panellists for their
commitment and contribution to the programme, to The Breast
and CancerWorld for their partnership in this initiative.
CME Accreditation and Certificates
Organisational Team
The event has been accredited by the
European Accreditation Council for Continuing
Medical Education (EACCME) to provide the
following CME activity for medical specialists.
The EACCME is an institution of the European
Union of Medical Specialists (UEMS). The
evaluation of the event has been performed
by the Accreditation Council of Oncology in Europe (ACOE) that
acknowledged the quality of the scientific programme and its
educational value.
Abstract submission
Dolores Knupfer (2)
[email protected]
Registration
Register online at
www.abc-lisbon.org
Luis Carvalho (2)
[email protected]
Laura Richetti (2)
[email protected]
Accommodation and Optional tours
Helder Carvalho (3)
[email protected]
Organisation
Chatrina Melcher (2)
[email protected]
Programme Secretariat
Dolores Knupfer (2)
[email protected];
Alexandra Zampetti (2)
[email protected]
Exhibition, satellite symposia and sponsorship
Francesca Marangoni (1)
[email protected]
Communication
Gabriele Maggini (2)
[email protected]
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Participants will be entitled to receive a certificate of
attendance at the close of the Conference by completing the
online evaluation questionnaire.
The event is designated for a maximum of
12 European CME credits (ECMEC).
Through an agreement between UEMS and
the American Medical Association, physicians
may convert EACCME credits to an equivalent
number of AMA PRA Category 1 Credits™.
Furthermore, the conference
has been accredited with 11 ESMOMORA category 1 points.
General Information / The Breast 24 S3 (2015) S2–S3
S3
Third Party Media Policy
Abstract Book
The policy applies to all activities related to the news media
during or in connection with ABC3 and is posted at www.abclisbon.org/pagine-interne/third-party-media-policy.html.
The aim is to ensure that information distributed to the
journalists is accurate and is issued at the correct times, complying
with any embargoes that may be in place.
The policy applies to media events that are organised at the ABC3
venue and off-site, and all third parties are requested to adhere.
This book includes abstracts submitted by the invited speakers
and those proposed by the participants that were accepted for
oral presentation, poster presentation or publication.
Abstracts were received for seven categories:
• Advanced breast cancer – Basic and translational research
• Advanced breast cancer – Nursing and advocacy
• Advanced breast cancer – Clinical issues: Medical oncology
• Advanced breast cancer – Clinical issues: Radiation oncology
• Advanced breast cancer – Clinical issues: Surgical oncology
• Advanced breast cancer – Clinical issues: Supportive and
palliative care
• Advanced breast cancer – Clinical issues: Other topics
A prefix has been added to the abstract number to identify the
type of presentation or acceptance:
IN: Abstracts submitted by the invited speakers
OR: Abstracts accepted for oral presentations
BP: Abstracts accepted as best poster presentations
PO: Abstracts accepted for poster presentations
PR: Abstracts accepted for inclusion in the abstract book
(not presented at the conference)
The Breast 24 S3 (2015) S4
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
High Patronage
The European School of Oncology is proud to announce that the Conference is held under the High
Patronage of His Excellency the President of the Portuguese Republic and that Mrs. Maria Cavaco Silva,
First Lady of the Portuguese Republic will welcome ABC3 participants to Lisbon and open the Conference.
Endorsement and Auspices
ESO is pleased to announce that also the ABC3 guidelines will be developed jointly by ESO and ESMO and
published simultaneously in The Breast and Annals of Oncology journals.
Furthermore, the ABC3
conference is endorsed by:
FEDERACIÓN
LATINOAMERICANA
DE MASTOLOGIA
held with support from
is CME accredited by
under the auspices of
and
FEDERACIÓN
The ABC3 guidelines are
LATINOAMERICANA
DE MASTOLOGIA
endorsed by
The ABC3 faculty includes
official representatives
appointed by
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
labelled
and will be submitted
for endorsement to
The Breast 24 S3 (2015) S5
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Sponsors (as of September 2015)
ESO wishes to extend its appreciation to the following sponsors for having granted their participation and support to ABC3:
Travel grants, support to the conference and to the patient advocacy activities
Participating organisations and companies
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
The Breast 24 S3 (2015) S6–S7
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Award
ABC Award
The ABC Award is aimed at recognising a researcher, physician,
nurse or patient advocate who has made an outstanding and
impacting contribution in the field of advanced breast cancer
throughout his/her career.
The first ABC Award - in recognition of his work on discovering
fundamental, clinically-relevant biological and molecular
mechanisms for metastases including site specificity, latency,
self-seeding and the role of the microenvironment in colonization
and drug resistance - was assigned to Joan Massagué.
ESO is pleased to announce that, in recognition for his work on
metastatic breast cancer, especially improving the management
of metastatic cancer to bone, resulting in preservation and
improvement in quality of life of patients worldwide, the second
ABC Award - will be assigned to Robert E. Coleman.
The Award Ceremony and Lecture are scheduled on Thursday,
5 November at 17:40.
ABC3 Award selection committee
Monica Castiglione, Department of Medicine, Geneva University,
Geneva, CH
Gabriel N. Hortobagyi, Department of Breast Medical Oncology,
The University of Texas MD Anderson Cancer Center, Houston,
US
Musa Mayer, AdvancedBC.org, New York, US
Chairs and Panel Members
Chairs
Fatima Cardoso, Breast Cancer Unit, Champalimaud Cancer
Center, Lisbon, PT
Alberto Costa, Scientific Director, European School of Oncology,
Milan, IT and Bellinzona, CH
Larry Norton, Breast Cancer Programs, Memorial SloanKettering Cancer Centre, New York, US
Eric P. Winer, Breast Oncology Center, Dana-Farber Cancer
Institute, Boston, US
Faculty and Panel Members
Matti S. Aapro, IMO Clinique De Genolier, Institut
Multidisciplinaire d'Oncologie, Genolier, CH
Fabrice André, Department of Medical Oncology,Gustave Roussy
Institute, Villejuif, FR
Sam Aparicio, Department of Breast and Molecular Oncology,
University of British Columbia and the BC Cancer Agency,
Vancouver, CA
Carlos H. Barrios, Department of Medicine, PUCRS School of
Medicine, Porto Allegre, BR
Marc Beishon, Cancer World, London, UK
Jonas Bergh, Department of Oncology Pathology, Karolinska
Institute, Stockholm, SE
Gouri S. Bhattacharyya, Department of Medical Oncology, Fortis
Hospital, Kolkata, IN
Laura Biganzoli, Department of Medical Oncology, Sandro
Pitigliani Oncology Centre, Prato, IT
Maria João Cardoso, Breast Unit, Champalimaud Cancer Center
and MamaHelp, Lisbon, PT
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Lisa A. Carey, Department of Hematology and Oncology, UNC
Lineberger Comprehensive Cancer Center, North Carolina, US
Sarbani Chaudhuri, Pfizer Oncology, New York, US
Robert E. Coleman, Academic Unit of Clinical Oncology, University
of Sheffield & Weston Park Hospital, Sheffield, UK
Dian “CJ” M. Corneliussen-James, METAvivor Research and
Support, Annapolis, US
Giuseppe Curigliano, Division of Experimental Therapeutics,
European Institute of Oncology, Milan, IT
Véronique Dieras, Department of Medical Oncology, Institut
Curie, Paris, FR
Nagi S. El Saghir, NK Basile Cancer Institute, American University
of Beirut Medical Center, Beirut, LB
Alexander Eniu, Department of Breast Tumors, Cancer Institute "I.
Chiricuta", Cluj-Napoca, RO
Lesley Fallowfield, Sussex Health Outcomes Research & Education
in Cancer, Brighton & Sussex Medical School, University of
Sussex, Brighton, UK
Doris Fenech, Breast Care Support Group, Europa Donna Malta,
Mtarfa, MT
Patrick Flamen, Department of Nuclear Medicine, Jules Bordet
Institute, Brussels, BE
Prudence A. Francis, Division of Cancer Medicine, Peter
MacCallum Cancer Centre, Melbourne, AU
Karen Gelmon, Department of Medical Oncology, BC Cancer
Agency, Vancouver, CA Alessandra Gennari, Department of Medical Oncology, Galliera
Hospital, Genoa, IT
Nadia Harbeck, Breast Center, University of Munich, Munich, DE
Jens Hoffmann, EPO Experimental Pharmacology & Oncology
Berlin-Buch GmbH, Berlin, DE
Chairs and Panel Members / The Breast 24 S3 (2015) S6–S7
Clifford A. Hudis, Breast Medicine Service/Medicine, Memorial
Sloan-Kettering Cancer Centre, New York, US
Bella Kaufman, Department of Oncology, Sheba Medical Center,
Tel Hashomer, IL
Ian E. Krop, Breast Oncology Center, Dana-Farber Cancer Institute,
Boston, US
Stella Kyriakides, Europa Donna Cyprus, Nicosia, CY
Musa Mayer, AdvancedBC.org, New York, US
Hanneke Meijer, Department of Radiation Oncology, Radboud
University Medical Center, Nijmegen, NL
Shirley A. Mertz, Metastatic Breast Cancer Network US, Inverness,
US
Shinji Ohno, Breast Oncology Center, Institute Hospital, Tokyo, JP
Olivia Pagani, Breast Unit, Oncology Institute of Southern
Switzerland, Bellinzona, CH
Evi Papadopoulos, Europa Donna, Nicosia, CY
Fedro A. Peccatori, Deputy Scientific Director, European School of
Oncology, Milan, IT and Bellinzona, CH
Frédérique Penault-Llorca, Department of Pathology, Jean Perrin
Centre, Comprehensive Cancer Centre, Clermont Ferrand, FR
Martine J. Piccart, Department of Medicine, Jules Bordet Institute,
Brussels, BE
Jean-Yves Pierga, Department of Medical Oncology, Institut Curie,
Paris Cancer Center, Paris, FR
Fausto Roila, Department of Medical Oncology, Monteluce
Policlinic, Perugia, IT
S7
Hope S. Rugo, Breast Oncology and Clinical Trials Education,
UCSF Helen Diller Family Comprehensive Cancer Center, San
Francisco, US
Kimberly A. Sabelko, Susan G. Komen, Dallas, US
Elzbieta Senkus-Konefka, Department of Oncology and
Radiotherapy, Medical University of Gdansk, Gdansk, PL
Lillie D. Shockney, Depts of Surgery and Oncology, Johns Hopkins
Breast Center, Baltimore, US
George W. Sledge, Division of Oncology, Stanford School of
Medicine, Stanford, US
Danielle Spence, Breast Cancer Network Australia, Camberwell,
AU
Richard Sullivan, Conflict & Health Research Program, Institute of
Cancer Policy, London, UK
Sandra M. Swain, Washington Cancer Institute, MedStar
Washington Hospital Center, Washington DC, US
David G. Taylor, School of Pharmacy, University College London,
London, UK
Christoph Thomssen, Clinic for Gynaecology, Martin-LutherUniversität, Klinikum Kröllwitz, Halle (Saale), DE
Luzia Travado, Department of Psycho-Oncology, Champalimaud
Clinical Centre, Lisbon, PT
Andrew Tutt, Breakthrough Breast Cancer Research Unit, King’s
College London and Guy’s and St Thomas’ NHS Foundation
Trust, London, UK
Daniel A. Vorobiof, Sandton Oncology Centre, Johannesburg, ZA
Binghe Xu, Department of Medical Oncology, Chinese Academy of
Medical Sciences & Peking Union Medical College, Beijing, CN
The Breast 24 S3 (2015) S8
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Breast Cancer Patient Advocacy Programme
Representatives of breast cancer patient advocacy groups are
warmly invited to participate in ABC3 and actively contribute to
the scientific programme and consensus sessions.
Furthermore, in collaboration with several leading breast
cancer patient advocacy groups worldwide, specific additional
patient advocacy have been scheduled.
Breast Cancer Patient Advocacy Committee
Coordinator:
Fatima Cardoso, Breast Cancer Unit, Champalimaud Cancer Center, Lisbon, PT
Marc Beishon, Cancer World, London,UK
Maria João Cardoso, MamaHelp, Lisbon, PT
Dian “CJ” M. Corneliussen-James, METAvivor Research and
Support, Annapolis, US
Musa Mayer, AdvancedBC.org, New York, US
Shirley A. Mertz, Metastatic Breast Cancer Network US,
Inverness, US
Evi Papadopoulos, Europa Donna, Nicosia, CY
Danielle Spence, Breast Cancer Network Australia, Camberwell,
AU
Kimberly A. Sabelko, Susan G. Komen, US
Breast Cancer Patient Advocacy Sessions (see pages S13 to S15 for full session details)
Thursday, 5 November 2015
9:00-10:30
Worldwide survey and call to action Chairs: F. Cardoso, PT and
D. “CJ” M. Corneliussen-James, US
10:30-11:00
S. Ginsberg, CA and A. Craig, CA
“I am Anna” Video presentation and viewing
11:00-12:30
Specific issues of young women with advanced breast cancer
Chairs: E. Papadopoulos, CY and
D. Spence, AU
16:15-16:40
“I am Anna” Q+A session
based on the video screened in the morning
S. Ginsberg, CA and A. Craig, CA
18:00-19.30
Advanced breast cancer symptom control
Chairs: M.J. Cardoso, PT and S.A. Mertz. US
Friday, 6 November 2015
18:30-19:30
ABC Advocacy: Wrap-up and Call to Action
Chairs: M. Beishon, UK and M. Mayer, US
Saturday, 7 November 2015
11:00-11:15 Report from the ABC Patient Advocacy Committee
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
S.A. Mertz, US
The Breast 24 S3 (2015) S9–S13
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Programme
Thursday, 5 November 2015
9:00-10:30
Breast cancer patient advocacy session:
Worldwide survey and call to action
Chairs: F. Cardoso, PT and D. “CJ” M. Corneliussen-James, US
09:00
Welcome and Introduction
D. “CJ” M. Corneliussen-James, US
09:05
The mBCVision 2025 Project: Why, how and what?
S. Chaudhuri, US
09:20
Main findings of the mBCVision 2025 Project
F. Cardoso, PT
09:45
Main findings of the mBCVision 2025 Project: implications for
patients
D. “CJ” M. Corneliussen-James, US
10:05
Discussion on Call to Action points
F. Cardoso, PT and D. “CJ” M. Corneliussen-James, US
9.00-10:30
Sponsored satellite symposium 1
To be confirmed (see page 17)
10:30-11:00
Coffee break
10:30-11:00
Breast cancer patient advocacy session
“I am Anna” Video presentation and viewing
S. Ginsberg, CA and A. Craig, CA
11:00-12:30
Breast cancer patient advocacy session:
Specific issues of young women with advanced breast cancer
Chairs: E. Papadopoulos, CY and D. Spence, AU
11:00
Introduction
E. Papadopoulos, CY
11:15
Presentation of key issues
L. Travado, PT
•
•
•
Relationships/ sexuality/personality/social image – how
women relate to themselves, their partners and their social
networks
Practical issues- work, finances, home support, including
childcare
Emotional concerns of those close to you, including children,
partners, parents
11:35
What are the requirements to assist women to address these
issues?
D. Spence, AU
11:55
Empowering women
S. Kyriakides, CY
12:10
Q+A session
D. Spence, AU
12:25
Closing remarks
D. Spence, AU
11:00-12:30
Sponsored satellite symposium 2
(see page 17)
12:30-13:30
Lunch
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
S10
Programme / The Breast 24 S3 (2015) S9–S13
13:30-14:25
Opening session
Chairs: F. Cardoso, PT and L. Norton, US
13:30
Welcome to Lisbon
M. Cavaco Silva, First Lady of the Portuguese Republic
13:40
Opening and introduction
F. Cardoso, PT
14:00
Keynote lecture: METAvivor: fighting prejudice! [abstract IN02]
D. “CJ” M. Corneliussen-James, US
14:25-15:30
Optimal management of HER-2+ ABC
Chairs: S. Ohno, JP and E.P. Winer, US
14:25
Is there an optimal treatment sequence?
14:40
Resistance to anti-HER-2 agents: what's new [abstract IN04]
I.E. Krop, US
14:55
Long term survivors specific issues [abstract IN05]
K. Gelmon, CA
15:10
Long term survivors: living on borrowed time [abstract IN06]
S.A. Mertz, US
15:25
Discussion
15:30-16:15
Best abstract presentations
Chairs: A. Costa, IT/CH and K.A. Sabelko, US
15:30
Unmet psychosocial and quality of life needs of patients living
with metastatic breast cancer (abstract OR37)
M. Hurlbert, US
15:45
No impact of increasing symptoms on quality of life?
Longitudinal data from the German MALIFE-Project on patients
receiving monochemo- and endocrine treatment for advanced
breast cancer – results from the TMK registry group (abstract
OR51)
N. Marschner, DE
16:00
CTL and IgG response to tumor-associated antigens as predictive
factors of therapeutic peptide vaccination for patients with
metastatic recurrent breast cancer (abstract OR128)
U. Toh, JP
16:15-16:40
Coffee break
16:15-16:40
Breast cancer patient advocacy session
“I am Anna” Q+A session based on the video screened in the
morning (*)
[abstract IN03]
S.M. Swain, US
S. Ginsberg, CA and A. Craig, CA
* “I am Anna”:
The video tells the insightful story of Anna Craig: a mother, wife,
artist, architect and young woman living with metastatic breast
cancer. The film follows Anna’s inspiring journey to create her
legacy by building an addition to her house that fulfils her artistic
dreams and leaves something special for her family. Through
this process we also watch her help to build a support network
for young metastatic women. I AM ANNA is produced by Rethink
Breast Cancer.
The video is screened in the morning and, in the afternoon, the
presenters will hold a questions and answers session.
16:40-17:40
New drugs, new side effects
Chairs: E. Papadopoulos, CY and E. Senkus-Konefka, PL
16:40
Endocrine [abstract IN07]
A. Eniu, RO
16:55
Pulmonary [abstract IN08]
H.S. Rugo, US
17:10
Immunologic alterations [abstract IN09]
C.H. Barrios, BR
17:25
The role of Patient Reported Outcomes [abstract IN10]
L. Fallowfield, UK
17:40-18:00
ABC Award and Lecture: Living with metastatic bone disease –
the positive impact of bone-targeted treatments [abstract IN1 ]
Chair: L. Norton, US
Awardee: R.E. Coleman, UK
Programme / The Breast 24 S3 (2015) S9–S13
18:00-19:30
Breast cancer patient advocacy session:
Advanced breast cancer symptom control
Chairs: M.J. Cardoso, PT and S.A. Mertz. US
18:00
Pain medication: Is it universally available to ABC Patients?
Is it a patient and/or human right in ABC?
A. Eniu, RO
18:20
Discussion
M.J. Cardoso, PT and S.A. Mertz. US
18:45
Barriers to Active Patient Reporting of Quality of Life
Symptoms/Outcomes In the ABC Setting
L. Fallowfield, UK
19:05
Discussion
M.J. Cardoso, PT and S.A. Mertz. US
18:00-19:30
Sponsored satellite symposium 3
(see page 17)
19:30
Welcome cocktail
Friday, 6 November 2015
9:00-10:00
Revolutionizing ER+ ABC management
Chairs: M.J. Piccart, BE and B. Xu, CN
9:00
The role of CDK and PI3K/mTOR inhibitors [abstract IN12]
F. André, FR
9:20
ESR1 and other suspects in resistance [abstract IN13]
V. Dieras, FR
9:35
Is ovarian ablation mandatory in pre-menopausal ER+ ABC
patients? [abstract IN14]
J. Bergh, SE
9:50
Discussion
10:00-10:30
Coffee break
10:30-11:35
Triple negative: is hope around the corner?
Chairs: N.S. El Saghir, LB and E.P. Winer, US
10:30
Current optimal management [abstract IN15]
L.A. Carey, US
10:45
Resurrecting PARP inhibition [abstract IN16]
A. Tutt, UK
11:00
Can immune-based therapies be the key? [abstract IN17]
G. Curigliano, IT
11:15
The role of androgen receptor and its inhibitors [abstract IN18]
C.A. Hudis, US
11:30
Discussion
11:35-12:05
New technologies and new techniques
Chairs: L.A. Carey, US and F.A. Peccatori, IT
11:35
New tools in nuclear medicine: what can they offer for ABC
patients [abstract IN19]
P. Flamen, BE
11:50
New radiotherapy techniques: application in ABC [abstract IN20]
H. Meijer, NL
12:05
Discussion
12:10-12:40
Supportive and palliative care
Chairs: L. Biganzoli, IT and D. Spence, AU
12:10
Optimal management of fatigue [abstract IN21]
F. Roila, IT
12:25
Dyspnea: the hardest symptom to control? [abstract IN22]
M.S. Aapro, CH
12:40
Discussion
12:45-13:45
Lunch and poster session (details are available on page 21)
S11
S12
Programme / The Breast 24 S3 (2015) S9–S13
13:45
Biology, biology, biology!
Chairs: L. Norton, US and F. Penault-Llorca, FR
13:45
Circulating tumor cells and tumor DNA: are liquid biopsies a
dream? [abstract IN23]
J.Y. Pierga, FR
14:05
Intra-tumor heterogeneity: challenges and solutions [abstract
IN24]
S. Aparicio, CA
14:25
Patient xenograph models: can an "avatar" help? [abstract IN25]
J. Hoffmann, DE
14:40-15:45
Clinical dilemma’s in ABC
Chairs: B. Kaufman, IL and D.A. Vorobiof, ZA
14:40
Biopsy, rebiopsy and dealing with discordant results [abstract
IN26]
N. Harbeck, DE
14:55
Is there an optimal sequence of systemic anticancer agents?
[abstract IN27]
P.A. Francis, AU
15:10
Until when should ABC be treated? [abstract IN28]
A. Gennari, IT
15:25
Surgery of the primary tumor: should the recommendation be
changed? [abstract IN29]
M.J. Cardoso, PT
15:40
Discussion
15:45-16:15
Coffee break
16:15-17:00
Survivorship in ABC
Chairs: D. Fenech, MT and C. Thomssen, DE
16:15
What are the main issues? [abstract IN30]
O. Pagani, CH
16:30
Addressing the needs of ABC patients [abstract IN31]
L.D. Shockney, US
16:45
Surviving ABC: the patient voice [abstract IN32]
E. Papadopoulos, CY
17:00-18:00
Affordability and access to care
Chairs: F. Cardoso, PT and M. Mayer, US
17:00
The cost of advanced breast cancer [abstract IN33]
R. Sullivan, UK
17:15
Are drugs really the main issue? [abstract IN34]
D.G. Taylor, UK
17:30
Can we really apply international guidelines in limited resources
countries? [abstract IN35]
G.S. Bhattacharyya, IN
17:45
Is a two-speed (rich vs poor) oncology inevitable? [abstract IN36] G.W. Sledge, US
18:00-19:30
Breast cancer patient advocacy session:
ABC Advocacy: Wrap-up and Call to Action
18:00-19:30
Sponsored satellite symposium 4
(see page 21)
Chairs: M. Beishon, UK and M. Mayer, US
Saturday, 7 November 2015
8:30-10:30
Consensus session (part I)
10:30-11:00
Coffee break
11:00-11:15
Report from ABC Patient Advocacy Committee
S.A. Mertz, US
11:15-12:45
Consensus session (part II)
ABC3 Chairs and Panellists
12:45-13:00
Close
A/V Recording during the Conference is prohibited.
ABC3 Chairs and Panellists
Programme / The Breast 24 S3 (2015) S9–S13
Consensus Panellists (September 2015)
Matti S. Aapro, CH
Fabrice André, FR
Carlos H. Barrios, BR
Jonas Bergh, SE
Gouri S. Bhattacharyya, IN
Laura Biganzoli, IT
Fatima Cardoso, PT
Maria Joao Cardoso, PT
Alberto Costa, CH/IT
Dian ”CJ” Corneliussen-James, US
Giuseppe Curigliano, IT
Véronique Dieras, FR
Nagi S. El Saghir, LB
Alexander Eniu, RO
Lesley Fallowfield, UK
Doris Fenech, MT
Patrick Flamen, BE
Prudence A. Francis, AU
Karen Gelmon, CA
Alessandra Gennari, IT
Nadia Harbeck, DE
Clifford A. Hudis, US
Bella Kaufman, IL
Musa Mayer, US
Hanneke Meijer, NL
Shirley A. Mertz, US
Larry Norton, US
Shinji Ohno, JP
Olivia Pagani, CH
Evi Papadopoulos, CY
Fedro A. Peccatori, IT
Frédérique Penault-Llorca, FR
Martine J. Piccart, BE
Jean-Yves Pierga, FR
Hope S. Rugo, US
Elzbieta Senkus-Konefka, PL
Lillie D. Shockney, US
George W. Sledge, US
Sandra M. Swain, US
Christoph Thomssen, DE
Andrew Tutt, UK
Daniel A. Vorobiof, ZA
Eric P. Winer, US
Binghe Xu, CN
S13
The Breast 24 S3 (2015) S14–S15
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Sponsored satellite symposia (as of September 2015)
Thursday, 5 November 2015
9:00-10:30
Sponsored satellite symposium 1 - To be confirmed
11:00-12:30
Sponsored satellite symposium 2
Novartis Oncology
Treatment strategies for optimizing the treatment experience
for patients with advanced breast cancer: shared decisionmaking and effective clinical management
Chair: J. Cortés, ES
11:00
Welcome and introduction
J. Cortés, ES
11:05
Pathways to endocrine resistance in HR+ aBC
G. Arpino, IT
11:20
Dual blockade strategies to enhance endocrine sensitivity in HR+
aBC
T. Bachelot, FR
11:45
Maximizing treatment benefit from dual blockade in HR+ aBC
J. Cortés, ES
12:10
The changing landscape of HR+ aBC
G. Arpino, IT
12:20
Interactive panel discussion and close
All speakers
Symposium faculty:
Grazia Arpino, University of Naples Federico II, Naples, IT
Thomas Bachelot, Centre Léon-Berard, Lyon, FR
Javier Cortés, Vall d’Hebron University Hospital, Barcelona, ES
18:00-19:30
Sponsored satellite symposium 3
Pfizer Oncology
Advances in ER+ HER2- breast cancer: targeting the cell cycle
Chair: A. Di Leo, IT
18:00
Welcome and introduction
A. Di Leo, IT
18:10
Improving outcomes in metastatic breast cancer patients:
changing perceptions
J. Gralow, US
18:30
Metastatic breast cancer: beyond standard endocrine therapy
J. Crown, IR
18:50
New treatment algorithms: focusing on patients’ needs
A. Llombart-Cussac, ES
19:20
Closing remarks and Q&A
All speakers
Symposium faculty:
John Crown, National Institute for Cellular Biotechnology, Dublin City University, Dublin, IR
Angelo Di Leo, Istituto Toscano Tumori, Hospital of Prato, Prato, IT
Julie Gralow, Seattle Cancer Care Alliance, University of Washington, Seattle, US
Antonio Llombart-Cussac, Hospital Arnau de Vilanova, Valencia, ES
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Sponsored satellite symposia / The Breast 24 S3 (2015) S14–S15
Friday, 6 November 2015
18:00-19:30
Sponsored satellite symposium 4
Eisai
What’s new since ABC2? Recent advances in chemotherapy for
ABC
Chair: X. Pivot, FR
Moderator: E.C. Antoine, FR
18:00
Welcome and introductions
X. Pivot, FR
18:05
Decision making in chemotherapy: where are we now?
X. Pivot, FR
18:25
New data for a new authorisation in second-line ABC
E.C. Antoine, FR
18:45
From clinical trials to clinical practice - level of evidence
J.M. Grouin, FR
19:10
Panel discussion and conclusions
All speakers
Symposium faculty:
Eric-Charles Antoine, Institut du Sein – Henri Hartmann, Paris, FR
Jean-Marie Grouin, Université de Rouen, Rouen, FR
Xavier Pivot, Centre Hospitalier Universitaire, Hôpital Jean Minjoz, Besançon, FR
S15
The Breast 24 S3 (2015) S16–S17
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Abstract Presenters
Sala Abdalla, University Hospital Lewisham, Department of
General Surgery, London, UK
Roberto Agresti, Istituto Nazionale dei Tumori, Breast Surgery
Unit, Milano, IT
Medhat M. Anwar, Medical Research Institute University of
Alexandria, Experimental and Clinical Surgery Department,
Alexandria, EG
Rania Azmi, “Survive & Thrive” Initiative, For Cancer Patients
Support, Salmiya, KW
Thomas Bachelot, Centre Léon Bérard, Breast Cancer Unit and
Clinical Trial Unit, Lyon FR
Francesca Balena, Europa Donna Italia, MBC Working Group,
Milano, IT
Jodie E. Battley, Cork University Hospital, Medical Oncology,
Cork, IE
Carol Ann Benn, Helen Joseph Breast Care Clinic, Johannesburg
ZA and University of the Witwatersrand, Faculty of Health
Sciences, Department of Surgery, Johannesburg, ZA
Narjiss Berrada, National Institute of Oncology, Medical
Oncology Department, Rabat, MA
Rita Canario, Instituto Português de Oncologia de Coimbra
Francisco Gentil, Medical Oncology Department, Coimbra, PT
Marina Elena Cazzaniga, San Gerardo Hospital, Medical
Oncology Department, Monza, IT
Niya Chari, Canadian Breast Cancer Network, Government
Relations, Ottawa, CA
Helen L. Coons, Women's Mental Health Associates, Health
Psychology, Denver, US
Maria Rita Dionisio, Hospital de Santa Maria CHLN Lisboa, Dept.
of Medical Oncology, Lisbon and IPATIMUP and Instituto de
Investigação e Inovação em Saúde, Cancer Genetics, Porto, PT
Mahmoud A. Elhussini, Alexandria Faculty of Medicine, Surgical
Oncology Unit, Alexandria, EG
Fadi Farhat, Saint Joseph University, Faculty of MedicineHematology-Oncology, Beirut, LB
Diana Freitas, Hospital de Braga, Medical Oncology Department,
Braga, PT
Miwa Fujihara, Hiroshima City Hiroshima Citizens Hospital,
Breast Surgery, Moto-machi, Naka-ku, Hiroshima, JP
Shawna Ginsberg, Rethink Breast Cancer, Breast Cancer
Department, Toronto, CA
Uwe Güth, Cantonal Hospital Winterthur, Obstetrics &
Gynecology, Winterthur, CH and University Hospital Basel,
Gynecology & Obstetrics, Basel, CH
Wirsma A. Harahap, Medical Faculty Andalas University/Dr. M.
Djamil Hospital, Department of Surgery, Padang, ID
Emily Harrold, Cork University Hospital, Medical Oncology
Department, Cork, IE
Shoko Hayama, Chiba University, General Surgery Department,
Chiba City, Japan, JP
Amany Helal, National Cancer Institute, Medical Oncology,
Cairo, EG
Reyhane Hoshyar, Birjand University of Medical Sciences,
Faculty of Medicine, Department of Biochemistry, Birjand, IR
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Marc Hurlbert, Avon Foundation for Women, Breast Cancer
Crusade, New York, US and Metastatic Breast Cancer Alliance,
Advocacy, New York, US
Jamshid Ibragimov, National Cancer Research Center,
Chemotherapy Department, Tashkent, UZ
Hiroki Ito, Kyorin University Hospital, Breast Surgery
Department, Tokyo, JP
Toshiaki Iwase, Chiba University Hospital, Breast and Thyroid
Surgery, Chiba, JP
Sara Jansson, Lund University, of Clinical Sciences, Division of
Oncology and Pathology, Lund, SE
Lika Katselashvili, Research Institute of Clinical Medicine,
Department of Oncology, Tbilisi, GE
Yasuko Kikuchi, International University of Health and Welfare
Mita Hospital, Breast Center, Tokyo, JP
Susan Knox, Europa donna - The European Breast Cancer
Coalition, Milan, IT
Elena Kovalenko, Russian Scientific Oncological Center, Research
of New Antitumor Agents, Moscow, Russian Federation, RU
Christian M. Kurbacher, Gynecologic Center Bonn-Friedensplatz,
Gynecologic Oncology Department, Bonn, DE
Matteo Lambertini, IRCCS AOU San Martino-IST, Department of
Medical Oncology, U.O. Oncologia Medica 2, Genova, IT
Maria Leadbeater, Ashgate Hospice, Macmillan Clinical Nurse
Specialist Palliative Care, Old Brampton, Chesterfield, UK
Roman Liubota, National Medical University named after O.O.
Bogomolets, Oncology Department, Kiev, UA
Norbert Marschner, Praxis für interdisziplinäre, Onkologie
& Hämatologie, Interdisziplinäre Onkologie &
Hämatologie,Freiburg, DE
Michelle M. Martinez-Montemayor, Universidad Central del
Caribe School of Medicine, Department of Biochemistry,
Bayamon, PR
Kazuo Matsuura, Hiroshima Prefectural Hospital, Breast Surgery,
Hiroshima, JP
Lori Marx-Rubiner, METAvivor Research and Support, Annapolis,
US
Tahir Mehmood, Shaukat Khanum Memorial Cancer Hospital
and Research Centre, Radiation Oncology, Lahore, PK
Snezana Milosevic, Institute for Oncology and Radiology of
Serbia, Daily Hospital for Chemotherapy, Belgrade, RS
Marijana Milovic-Kovacevic, Institute for Oncology and
Radiology of Serbia, Department of Medical Oncology,
Belgrade, RS
Giacomo Montagna, Ente Ospedaliero Cantonale, Department
of Obstetrics and Gyneacology and Breast Unit of Southern
Switzerland (CSSI), Lugano, CH
Serafin Murillo Morales, Hospital Universitari Arnau de Vilanova
de Lleida, Department of Medical Oncology, Lleida, ES
Rikiya Nakamura, Chiba Cancer Center Hospital, Breast Surgery,
Chuou Chiba, JP
Akimasa Nishimura, Hirosaki University, Surgery, Hirosaki, JP
Amanda Nobre Carvalho, Algarve Hospital Centre, Medical
Oncology Department, Faro, PT
Abstract Presenters / The Breast 24 S3 (2015) S16–S17
Connor O'Leary, Cork University Hospital, Department of
Medical Oncology, Cork, IE
Jose Pereira, Hospital Sao Francisco Xavier, Oncology and
Medical Departments, Lisbon, PT
Shankpal Pramod, Health Alert Organisation of India, Health
Department, Garud colony, Deopur, Dhule, IN
Nicoletta Provinciali, E.O. Ospedali Galliera, Division of Medical
Oncology, Genoa, IT
Prasanna Rammohan, Madras Medical College, Medical
Oncology, Chennai, Tamilnadu, IN
Ivica Ratosa, Institute of Oncology Ljubljana, Department of
Radiation Oncology, Ljubljana, SI
Hope S. Rugo, University of California San Francisco
Comprehensive Cancer Center, Hematology/Oncology, San
Francisco, US
Masako Sato, NHO Hokkaido Cancer Center, Breast Surgery,
Sapporo, Hokkaido, JP
Danielle Spence, Breast Cancer Network Australia, Camberwell,
Victoria, AU
Anna Sukhotko, Moscow P.A. Gerzen's Cancer Research
Institute – The National Medical Research Radiologic
Center of the Ministry of Health of the Russian Federation,
Department of Oncology and Reconstructive-plastic Surgery
of the Breast and Skin, Moscow, RU
Marie Sundquist, County Hospitals, Breast Unit Surgery, Kalmar,
SE
Medha Sutliff, Young Survival Coalition, National Programs, New
York, US
S17
Konstanta Timcheva, Women’s Health Hospital “Nadezhda”,
Medical Oncology Clinic, Sofia, BG
Anna Thulin, Institution of Clinical Sciences, Department of
Oncology, Gothenburg, SE
Uhi Toh, Kurume University School of Medicine, Department of
Surgery, Kurume, JP
Zoran Tomasevic, Institute for Oncology and Radiology of
Serbia, Daily Hospital, Belgrade, RS
Toshiaki Utsumi, Fujita Health University, Breast Surgery
Department, Aichi, Toyoake, JP
Marisse Venter, Breast Care Center of Excellence, Breast
Oncology, Johannesburg, ZA
Judy Vicente de Paolo, Portuguese Institute of Oncology,
Medical Oncology Department, Coimbra, PT
Neelima Vidula, University of California, San Francisco,
Hematology/Oncology Department, San Francisco, US
Junichiro Watanabe, Shizuoka Cancer Centre, Breast Oncology
Department, Shizuoka, JP
Karolina Widera, Maria Skłodowska-Curie Memorial Cancer
Center and Institute of Oncology, Gliwice Branch, Outpatient
Clinic, Gliwice, PL
Rachel Würstlein, Medical Center of the Ludwig-MaximiliansUniversity, Department for Gynecology of Obstetrics and
Comprehensive Cancer Center of LMU, Munich, DE
Jun Yamamura, Sakai City Hospital, Breast Surgery Department,
Sakai City, JP
The Breast 24 S3 (2015) S18–S19
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Poster Session
BP38
BP52
BP103
BP129
PO39
PO40
PO41
PO42
PO43
PO44
PO45
PO46
PO47
PO48
PO53
PO54
PO55
PO56
PO57
PO58
PO59
PO60
PO61
PO62
PO63
PO64
PO65
PO66
PO67
PO68
PO69
PO70
PO71
PO72
PO73
Metastatic breast cancer in Canada: waiting for treatment. Niya Chari, CA
Is there a different treatment response between visceral and non-visceral metastatic breast cancer: a systematic literature review of
registration trials. Rachel Würstlein, DE
Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis. Roberto Agresti, IT
Insulin resistance (IR) and prognosis of metastatic breast cancer (MBC) patients. Nicoletta Provinciali, IT
Effective advocacy for women with metastatic breast cancer: a European perspective. Susan Knox, IT
Unmet needs of Australian women with metastatic breast cancer with financially dependent children: the consumer perspective. Danielle
Spence, AU
Middle Eastern ABC/MBC patients: overcoming the triple-burden of stigmatization, lack of information and recurrent illness. Rania Azmi,
KW
Make your dialogue count survey: addressing communication gaps between patients with advanced breast cancer, their caregivers and
oncologists and understanding information and emotional needs to improve treatment and side effect management. Helen L. Coons, US
“Fight, live, keep smiling”: the first Italian blog about metastatic breast cancer (MBC) addressed to the general public. A quali-quantitative
analysis of all the comments posted online on the blog of the Europa Donna Italia MBC Working Group. Francesca Balena, IT
In Our Shoes: raising the voices of MBC patients. Lori Marx-Rubiner, US
Information needs of young women with metastatic breast cancer to manage their treatment, side effects and clinical trials. Medha
Sutliff, US
I AM ANNA: Exploring metastatic breast cancer through the eyes of a young woman. Shawna Ginsberg, US
Identifying deficits and needs from stakeholders about palliative care issues. Shankpal Pramod, IN
Terminology used in advanced breast cancer and the need for consistency. Maria Leadbeater, UK
Clinical impact of metronomic oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic
breast cancer. Miwa Fujihara, JP
A retrospective multicenter observation study in metastatic breast cancer patients: comparative analysis on efficacy of eribulin mesylate
with taxane regimens (including combination with bevacizumab). Yasuko Kikuchi, JP
Efficacy and safety of eribulin in anthracycline and taxane-pretreated patients: Russian experience. Elena Kovalenko, RU
BOLERO-4: A phase 2, open-label, multicenter, single-arm trial investigating the efficacy and safety of first-line everolimus (EVE) in
combination with letrozole (LET) in postmenopausal patients (pts) with estrogen receptor–positive (ER+), human epidermal growth
factor receptor 2–negative (HER2-) metastatic or locally advanced unresectable breast cancer (BC). Thomas Bachelot, FR
Clinical efficacy of LH-RH analogue plus aromatase inhibitor in premenopausal women with estrogen receptor–positive advanced breast
cancer: a single-institution retrospective study. Toshiaki Utsumi, JP
Does previous neoadjuvant/adjuvant trastuzumab influence the disease outcome of metastatic HER2 positive breast cancer patients
treated with first line trastuzumab and chemotherapy. Snezana Milosevic, RS
Durable remissions with trastuzumab treatment for HER2 positive metastatic breast cancer – single center experience. Zoran Tomasevic,
RS
The role of lapatinib in the management of HER2-positive metastatic breast cancer: a review of a single institution’s experience during
the trastuzumab and lapatinib era. Junichiro Watanabe, JP
Oral vinorelbine in combination with trastuzumab as a first line therapy of metastatic or locally advanced Her2-positive breast cancer.
Fadi Farhat, LB
First line trastuzumab-based therapy in HER2-positive metastatic cancer patients presenting with de novo or recurrent disease: a
multicenter retrospective cohort study. Matteo Lambertini, IT
Cure in metastatic breast cancer: an aggressive approach does not appear to be the key to the black box. Uwe Güth, CH
Metronomic chemotherapy (CHT) combination of vinorelbine (VRL) and capecitabine (CAPE) in HER2- advanced breast cancer (ABC)
patients (pts) does not impair Global QoL. First results of the VICTOR-2 study. Marina Elena Cazzaniga, IT
Phase II trial of metronomic combination chemotherapy with oral regimen in heavily pretreated metastatic breast cancer. Prasanna
Rammohan, IN
Neoadjuvant chemotherapy for locally advanced breast cancer: a solution to avoid mastectomy Mahmoud A. Elhussini, EG
Neo-adjuvant hormonal therapy for locally advanced breast cancer. Lika Katselashvili, GE
Triple negative breast cancer - Neoadjuvant chemotherapy response evaluation with taxane/anthracycline protocol - Single centre 5 years
experience. Judy Vicente de Paolo, PT
Brachial plexopathy in metastatic breast cancer: a review of patient characteristics and diagnosis in an Irish tertiary referral centre.
Connor O'Leary, IE
Estrogen receptor as a negative predictor of complete pathological response in HER2 positive locally advanced breast cancer. Rita Canario,
PT
Monitoring therapy response in metastatic breast cancer using tumour markers CA15-3 and TPS. Marie Sundquist, SE
Therapeutic effect prediction based on biomarkers in the pleural effusion specimens of breast cancer patients. Rikiya Nakamura, JP
Outpatient catumaxomab therapy in metastatic breast cancer patients suffering from malignant effusions due to peritoneal or pleural
carcinomatosis: a single institution experience. Christian M. Kurbacher, DE
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Poster Session / The Breast 24 S3 (2015) S18–S19
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Which is more beneficial as an initial therapy for the first distant metastasis of breast cancer: chemotherapy or endocrine therapy for
hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients?: A single-center study. Jun
Yamamura, JP
The CTPET/MDST ratio: an introduction of a quantitative measure of effective palliative endocrine therapy in metastatic breast cancer.
Uwe Güth, CH
Therapeutic strategy for recurrent HER2-positive breast cancer patients. Akimasa Nishimura, JP
Locally advanced breast cancer In young female. The Egyptian National Cancer Institute experience. Amany Helal, EG
Elderly women and breast cancer: characterization of treatment practices. Diana Freitas, PT
Elderly metastatic breast cancer at diagnosis: a single institution experience. Amanda Nobre Carvalho, PT
Elevated neutrophil to lymphocyte ratio predicts worse survival outcome after recurrence for patients with triple negative breast cancer.
Toshiaki Iwase, JP
Compliance and persistence to palliative endocrine therapy in metastatic breast cancer. Uwe Güth, CH
Epidemiology and therapeutic management of metastatic breast cancer in Bulgaria: a retrospective cohort study. Konstanta Timcheva, BG
Current status of the management of advanced RH+/Her2- breast cancer in Morocco. Narjiss Berrada, MA
Characterisation of breast cancer brain metastases through a 21-year period – a study from the Swedish Association of Breast Oncologists
(SABO). Anna Thulin, SE
Brain metastases in HER2- positive breast cancer patients: a single institute experience. Tahir Mehmood, PK
Is brain metastases location associated with prognosis in breast cancer patients? Karolina Widera, PL
Treatment outcomes of breast cancer brain metastases. Ivica Ratosa, SI
IMRT-SIB for locally advanced inoperable breast cancer patients. Karolina Widera, PL
Prognostic factors after gamma knife radiosurgery in breast cancer patients with brain metastases. Shoko Hayama, JP
The surgical management of lung nodules in breast cancer patients. Kazuo Matsuura, JP
Success and failure of primary medical, non-operative management in patients who present with stage IV breast cancer. Uwe Güth, CH
N2 lymph nodes post-primary chemotherapy may predict recurrence in locally advanced breast cancer. Carol Ann Benn, ZA
Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer. Anna
Sukhotko, RU
Novel and safe techniques in immediate breast reconstruction for locally advanced breast cancer, particularly inflammatory breast cancer.
Marisse Venter, ZA
The impact of locoregional treatment of primary metastatic breast cancer. Roman Liubota, UA
Metastases of lobular breast carcinoma in the terminal ileum and ileocaecal valve. Sala Abdalla, UK
Efficacy of NEPA, the first combination antiemetic agent, in patients with breast cancer receiving anthracycline/cyclophosphamide (AC) or
non-AC chemotherapy. Hope Rugo, US
Using of hepatoprotectors in the drug treatment of patients with advanced breast cancer. Jamshid Ibragimov, UZ
The emotional toll of metastatic breast cancer on young women. Medha Sutliff, US
The last quarter of a honeymoon – A wedding’s story. Jose Pereira, PT
Can we make a portrait of women with inoperable locally advanced breast cancer? The experience of the Breast Unit of Southern
Switzerland (CSSI). Giacomo Montagna, CH
Sodium fluoride PET/CT: a superior imaging modality in evaluation of osseous metastatic disease. Emily Harrold, IE
Clinical utility of the expression of HER3, HER4, PTEN and IGF1R in HER2-positive advanced or metastatic breast cancer. Hiroki Ito, JP
Heterogeneity in the expression of hormone receptors and HER2 between the primary breast cancer and pulmonary metastasis. Masako
Sato, JP
Apoptotic activities of recombinant cell surface receptor fas within tumor microenvironment of breast carcinoma. Medhat M. Anwar, EG
Differential expression of plasma membrane proteins in inflammatory breast cancer via stable isotope labeled amino acids in culture
(SILAC). Michelle M. Martinez-Montemayor, PR
Analysis of primary breast cancer (BC) expression of programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) to
determine associations with clinical characteristics and outcomes. Neelima Vidula, US
At a glance the BRCAs epigenetic study in Padang, west Sumatera, Indonesia. Wirsma A. Harahap, ID
P-cadherin: a candidate biomarker for axillary-based breast cancer decisions in clinical practice. Maria Rita Dionisio, PT
Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence free survival and
development of bone metastases in the I-SPY 1 trial (CALGB 150007/150012; ACRIN 6657). Neelima Vidula, US
Changing in tumor biology of triple negative breast cancer between primary and metastatic lesions. Marijana Milovic-Kovacevic, RS
Sucessfull use of HER2 targeted agents in patients with heavily pretreated HER2-negative metastatic breast cancer presenting with
elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells. Christian M. Kurbacher, DE
Evolution of the expression of circulating tumor cells (CTC) and CK-19 mRNA (CK19) as prognostic factors in heavily pretreated metastatic
breast cancer. Serafin Murillo Morales, ES
Prognostic impact of circulating tumor cell clusters and apoptosis in metastatic breast cancer. Sara Jansson, SE
Synergistic antitumor effects of crocin combined with hyperthermia on breast cancer cells. Reyhane Hoshyar, IR
ICORG 13-01 ABC survey: are we meeting the needs of patients with advanced breast cancer (ABC) in Ireland? A nationwide survey. Jodie
E. Battley, IE
Disclaimer
No responsibility is assumed by the organisers for any injury and/or damage to persons or property as a matter of products liability, negligence or
otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the material herein. Organisers recommend that
independent verification of diagnoses, therapies and dosages should be made.
Every effort has been made to faithfully reproduce the materials as submitted. However, no responsibility is assumed by the organisers for any
omissions or misprints.
The Breast 24 S3 (2015) S21–S75
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Invited abstracts
IN01
LIVING WITH METASTATIC BONE DISEASE – THE POSITIVE IMPACT OF
BONE-TARGETED TREATMENTS
Robert Coleman
University of Sheffield, Yorkshire Cancer Research, Sheffield, UK
Bone metastases result from interactions between cancer cells in the
bone marrow microenvironment and normal bone cells, with receptor
activator of nuclear factor kappa B ligand (RANKL) a key mediator in
this process. Growth factors and cytokines secreted by tumour cells
stimulate stromal cells and osteoblasts to secrete RANKL, which, via
the RANK receptor, accelerates osteoclastic bone resorption, thereby
providing the rationale for bone-targeted osteoclast inhibitors as an
adjunct to specific anticancer agents to both prevent and treat bone
metastases.
Multiple, randomised controlled trials over the past two decades
have clearly demonstrated that bisphosphonates (BPs) are effective
in reducing skeletal morbidity from metastatic cancer and a recent
meta-analysis has helped define their role in the adjuvant setting. BPs
also relieve bone pain, and improve both the physical functioning and
quality of life of patients with metastatic bone disease. Zoledronic acid
is the most widely used agent and and has shown superior efficacy to
pamidronate in the prevention of skeletal complications in breast cancer.
Oral agents such as ibandronate and clodronate also provide a useful
alternative for some clinical situations. Now that these treatments are
well established, efforts are underway to maximise the risk-benefits
of treatment by reducing the frequency of treatment when clinically
appropriate. More recently denosumab, a fully humanised monoclonal
antibody that specifically inhibits RANKL, has become available and
been shown to be significantly more effective than zoledronic acid,
easier to administer and with some safety advantages.
Other bone-targeted agents are in development. Notably, radium-223,
a calcium mimic that preferentially targets bone metastases with highenergy alpha-particles has been approved for use in advanced prostate
cancer. In addition to positive effects on survival, radium delayed the
time to first symptomatic skeletal event over and above the effects of
a BP and had a positive impact on quality of life. Development of this
agent is now underway in advanced breast cancer.
In summary, bone-targeted agents are an important component of the
management of advanced malignancy. In combination with systemic
cancer therapy, effective symptom control and appropriate surgical and
radiological interventions, bone-targeted treatments have transformed
the care of patients with metastatic bone disease.
IN02
METAVIVOR: FIGHTING PREJUDICE
CJ (Dian) Corneliussen-James
Metavivor Research and Support Inc, Annapolis, USA
Background: A pervasive, positive breast cancer message that metastasis
can be avoided, that if caught early it can be “cured”, that only “older”
women are at risk and that all will be well if “a person does everything
right” has sent us down a path of late diagnoses, stigmatization of
patients, horrifically low funding for ABC research and is a disease
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
only of older women, is being beat, that those who metastasize are
themselves at fault, that that the disease, a desire to portray cancer as a
disease being conquered, a message that it is an old person’s disease, we
have organizations de endeavor to spread positive METAvivor is working
to change that.
Methods: Through international surveys and conferences, online discussion boards, meetings with cancer organizations, participation in
panels and interactions with thousands of ABC patients, discussions
with patients from around the world, past surveys.
Results: As if the challenges of the disease were not difficult enough,
ABC patients face additional prejudice on numerous fronts.
Medical: Many learn of their metastasis by phone or answering machine
and on the other learn by phone that nothing more can be done. Some
oncologists and other specialists make little effort for ABC patients,
having already written them off, and young patients with breast cancer
symptoms are often told they’re too young for breast cancer and denied
mammograms only to be diagnosed at stage IV.
Support: ABC-specific support programs are rare; all-stage support
programs tend to target early-stage and request ABC patients to not
mention their disease. Cancer organizations often lack ABC materials,
few have hotline-ready ABC experts, their conferences are often devoid
of ABC speakers and they continue to push pink on a community that
has largely rejected the color. ABC statistics are rare and often shaky.
Literature, slogans and talks by local and national health services, doctors
and cancer groups state breast cancer can be avoided or at least survived
by doing “everything right”, unwittingly implying ABC is the fault of the
patient. The public buys this making the concept pervasive. The media
prefers to avoid the subject altogether or represents the disease by
covering those doing well. Terminology is missing or confusing: Patients
are presumably “survivors” even while dying; “metastasis” research is
largely to “prevent” metastasis; the “cure” is illusive and rarely defined
but when it is does not relate to ABC; and a patient advocate is someone
who speaks for the patient, not a patient speaking for him/herself.
Everything combines to isolate and stigmatize a patient already facing
a devastating disease.
Conclusion: The issue must be addressed on numerous fronts. METAvivor
works with medical centers, research centers, hospitals, departments
of health, public forums, pharmaceutical and biotech companies, social
media, patients, caregivers, interested parties and others in an effort to
change the paradigm.
IN03
IS THERE AN OPTIMAL TREATMENT SEQUENCE FOR HER2 POSITIVE
ADVANCED BREAST CANCER?
Shagun Arora, Sandra M. Swain
Washington Cancer Institute, MedStar Washington Hospital Center,
Washington DC, USA
Trastuzumab has converted a once rapidly-lethal malignancy into one
with survival estimated in years [1,2]. Newer therapies are now in our
treatment armamentarium, prompting the publication of guidelines
by ASCO for HER2 driven advanced breast cancer (ABC) [3]. Is there
an optimal treatment sequence? CLEOPATRA, comparing first-line
docetaxel/trastuzumab/pertuzumab (THP) to placebo/docetaxel/
trastuzumab, showed an improvement in overall survival (OS) with
pertuzumab by 15.7 months; median OS reached 56.5 months [4,5].
S22
Abstracts / The Breast 24 S3 (2015) S21–S75
This created a new paradigm in HER2 driven ABC with THP as the firstline treatment of choice. A phase II trial, utilizing weekly paclitaxel with
trastuzumab/pertuzumab reported median progression free survival
(PFS) of 19.5 months [6]. These related regimens are being compared in
the PERUSE trial [NCT01572038]. MA.31 compared first-line lapatinib/
taxane to trastuzumab/taxane, with worse OS with lapatinib and no
difference in time to first CNS metastases suggesting that it should
not be used as first-line therapy [7]. Efficacy of T-DM1 in the first-line
setting is yet to be proven in the MARIANNE study.
Targeted second-line options include T-DM1 or lapatinib. EMILIA
showed improved survival with second-line T-DM1 versus lapatinib/
capecitabine with mOS of 30.9 versus 25.1 months [10]. Upon
progression through trastuzumab/pertuzumab, T-DM1 should be used.
Following second-line, sequencing is undefined and decision should
be patient-centric. If pertuzumab has not yet been utilized, its use is
recommended by ASCO [3]. TH3RESA showed efficacy in >3rd line T-DM1
in pre-treated ABC, with improvements in PFS from 3.3 to 6.2 months
[8]. A phase IIa trial of targeted HER2 pertuzumab and T-DM1 showed
efficacy [9]. EGF104900, comparing trastuzumab/lapatinib versus
lapatinib in heavily-pretreated patients who progress on trastuzumab,
showed improvement in mOS of 4.5 months with dual-HER2 blockade
[10,11]. These bring up two points: trastuzumab beyond progression
and synergism of dual-HER2 blockade and warrant further study. Other
combinations with chemotherapy such as navelbine are effective with
trastuzumab.
ABCs with co-expression of hormone receptor (HR) and HER2 are
common and clinical data dictates HER2 amplification leads to hormonal
therapy resistance [12]. The subset of patients who benefit solely from
HR/HER2 blockade is yet to be defined; clinicians may consider this in
highly selected patients. TAnDEM compared anastrazole/trastuzumab
versus anastrazole and showed improved PFS in the combination arm
(4.8 vs 2.4 months) but not in OS[13]; EGF30008 compared letrozole/
lapatinib versus letrozole and found similar PFS improvements (8.2 vs
3 months) [14]. ASCO guidelines state a first-line recommendation in
HR and HER2 positive ABC is HER2 targeted therapy with chemotherapy,
adding hormones upon the completion of chemotherapy, as PFS is much
shorter compared to the chemotherapy regimens as above [3].
A limitation in the use of HER2 directed therapies is potential decreased
cardiac function especially with previous anthracycline treatment;
SAFE-HEaRt [NCT01904903] is investigating optimizing cardiac function
concomitant with HER2 therapies, allowing patients to continue
to receive potentially life-prolonging treatment. Additional HER2
targeted TKI, neratinib, has shown significant clinical activity. Other
trials attempting to overcome trastuzumab resistance are ongoing:
MM-302, an antibody-drug conjugate in HERMIONE [NCT02213744];
MM-111, targeting HER2 and HER3 [NCT01097460]; PI3K inhibitors
[NCT01042925]; Hsp90 inhibitors with trastuzumab [NCT01271920];
the dual TKI/VEGFR inhibitor KD019 [NCT02154529]; and exploration of
vaccines and checkpoint inhibitors.
[1] Cobleigh, M., et al. Efficacy and safety of Herceptin as a single agent
in 222 women with HER2 overexpression who relapsed following
chemotherapy for metastatic breast cancer. in Proc Am Soc Clin
Oncol. 1998.
[2] Slamon, D.J., et al., Use of chemotherapy plus a monoclonal antibody
against HER2 for metastatic breast cancer that overexpresses HER2.
N Engl J Med, 2001;344:783-92.
[3] Giordano, S.H., et al., Systemic therapy for patients with advanced
human epidermal growth factor receptor 2-positive breast cancer:
American Society of Clinical Oncology clinical practice guideline. J
Clin Oncol, 2014;32:2078-99.
[4] Baselga, J., et al., Pertuzumab plus trastuzumab plus docetaxel for
metastatic breast cancer. N Engl J Med, 2012;366(2): p. 109-19.
[5] Swain, S.M., et al., Pertuzumab, trastuzumab, and docetaxel in HER2positive metastatic breast cancer. N Engl J Med, 2015;372:724-34.
[6] Dang, C., et al., Phase II study of paclitaxel given once per week
along with trastuzumab and pertuzumab in patients with human
epidermal growth factor receptor 2-positive metastatic breast
cancer. J Clin Oncol, 2015;33:442-7.
[7] Gelmon, K.A., et al., Lapatinib or Trastuzumab Plus Taxane Therapy
for Human Epidermal Growth Factor Receptor 2-Positive Advanced
Breast Cancer: Final Results of NCIC CTG MA.31. J Clin Oncol, 2015.
[8] Krop, I.E., et al., Trastuzumab emtansine versus treatment of
physician’s choice for pretreated HER2-positive advanced breast
cancer (TH3RESA): a randomised, open-label, phase 3 trial. Lancet
Oncol, 2014;15:689-99.
[9] Miller, K.D., et al., Phase IIa trial of trastuzumab emtansine with
pertuzumab for patients with human epidermal growth factor
receptor 2-positive, locally advanced, or metastatic breast cancer. J
Clin Oncol, 2014;32:1437-44.
[10] Blackwell, K.L., et al., Randomized study of Lapatinib alone or in
combination with trastuzumab in women with ErbB2-positive,
trastuzumab-refractory metastatic breast cancer. J Clin Oncol,
2010;28:1124-30.
[11] Blackwell, K.L., et al., Overall survival benefit with lapatinib in
combination with trastuzumab for patients with human epidermal
growth factor receptor 2-positive metastatic breast cancer: final
results from the EGF104900 Study. J Clin Oncol, 2012;30:2585-92.
[12] Pietras, R.J., et al., HER-2 tyrosine kinase pathway targets estrogen
receptor and promotes hormone-independent growth in human
breast cancer cells. Oncogene, 1995;10:2435-46.
[13] Kaufman, B., et al., Trastuzumab plus anastrozole versus anastrozole
alone for the treatment of postmenopausal women with human
epidermal growth factor receptor 2-positive, hormone receptorpositive metastatic breast cancer: results from the randomized
phase III TAnDEM study. J Clin Oncol, 2009;27:5529-37.
[14] Johnston, S., et al., Lapatinib combined with letrozole versus letrozole
and placebo as first-line therapy for postmenopausal hormone receptorpositive metastatic breast cancer. J Clin Oncol, 2009;27:5538-46.
IN04
OPTIMAL MANAGEMENT OF HER-2+ ABC
Ian E. Krop
Harvard Medical School, Dana-Farber Cancer Institute, Boston, USA
Amplification of the HER2/neu gene occurs in approximately 20%
of invasive breast cancers and is associated with aggressive clinical
behavior. The development of HER2-targeted therapies, including
trastuzumab, lapatinib, pertuzumab and trastuzumab emtansine
(T-DM1) has revolutionized the treatment of this disease, leading
to dramatic improvements in clinical outcomes. Given these
improvements, the goals in treating patients with advanced HER2positive breast cancer are to both extend survival as well as to minimize
toxicities of therapy. In patients with newly diagnosed metastatic breast
cancer, pertuzumab, in combination with trastuzumab and docetaxel,
markedly improves survival and only mildly increases toxicity compared
to trastuzumab and docetaxel. Pertuzumab, trastuzumab, and a taxane
should thus be considered the standard of care for most patients in
the first line setting. Endocrine therapy ± trastuzumab or lapatinib can
also be considered as first line therapy in select patients with hormone
receptor positive HER2+ ABC. In the second line setting, the antibodydrug conjugate T-DM1is the standard of care as it is associated with
longer survival and less toxicity than capecitabine and lapatinib. In 3rd
and later lines of therapy, continuation of HER2-directed therapy is
important, but there are no definitive data that a particular regimen (e.g.
trastuzumab + chemotherapy, lapatinib + chemotherapy, trastuzumab +
lapatinib) is superior in this setting. Thus decisions regarding choice of
therapy should be guided by patients’ preferences regarding toxicity
profiles and route of administration.
Although HER2-directed therapy has improved outcomes, resistance to
these agents eventually develops in almost all patients. CNS metastases
represent one increasingly common manifestation of treatment
resistance in HER2-positive cancers. Understanding mechanisms of
resistance and development of novel agents to overcome this resistance
is critical. A multitude of agents designed to overcome resistance are
currently being evaluated in the clinic including PI3-kinase inhibitors,
potent tyrosine kinase inhibitors, new antibody-drug conjugates, and
novel immunotherapies. In addition, studies evaluating the genomic
alterations present in metastatic HER2-positive cancer tissue are
beginning to provide clues as to the mechanisms of resistance present
Abstracts / The Breast 24 S3 (2015) S21–S75
in treatment refractory disease. It is possible that with continued
improvements in therapies and a better understanding of molecular
resistance mechanisms, mortality associated with metastatic HER2positive breast cancer can be dramatically reduced.
IN05
LONG TERM SURVIVAL WITH ADVANCED DISEASE. CHALLENGES FOR
THE PATIENT, THEIR SUPPORT SYSTEM AND CARE GIVERS
Karen Gelmon1,2, Sally Thorne2
1
BC Cancer Agency, Medical Oncology Dpt., Vancouver, Canada; 2University
of British Columbia, Medical Oncology Dept, Vancouver, Canada
Despite incurable and life-limiting metastatic conditions, many patients
are living longer with serious disease, pushing the boundaries of what
science explains and clinicians can confidently interpret using available
evidence. While this extension of good quality life is our goal, it creates
new challenges. The treatments may cause long term physical side
effects which were not described in the initial studies of the agents when
used for limited time periods. The therapies for these toxicities may be
variable and anecdotal, and need proper study. There may be signficant
psychological and spiritual issues for the long terms survivor including
uncertainty of the duration, the need to change their focus from ‘about
to die’ to ‘living with the disease long term’, and the issues of the value
of life. As well there may be substantial financial costs of long term
treatment and loss of income from continued unemployment. Insurance
companies may be less responsive to long term claims. For others there
may be continued employment but an inablility to make longterm
job commitments. For the family and friends there are the issues of
changing focus and living with someone who may or may not be well
long term but for whom their role in the family needs to be maintained
and possibly redefined. Caregivers need to change from a short term
palliative careplan to a chronic plan that remains non curative. Issues of
treatment vacations, quality of life, redefinition of ‘palliative’ goals and
psychological support need to be addressed with clear communcation
which may change as new evidence becomes available. The caregiver
who has delivered the sobering news of recurrent disease and its
inevitable end is now seeing a chronic patient and must ensure other
health needs are looked after appropriately, although what appropriate
is for a metastatic patient may vary.
To address these issues we did a study from an early subset of such
individuals within a longitudinal qualitative cancer cohort study on
clinician–patient communication across the cancer trajectory. We
contextualized experiential accounts of communication in a changing
environment of the costs and uncertainties of personalized medicine
for long term survivors, and examined the complex psychosocial
circumstances of this rapidly growing patient population. Interpretation
of these findings illustrates how emerging issues in cancer treatment
influence the experience of these patients, their social and support
networks, their cancer care specialists, and the multidisciplinary teams
charged with coordinating their care. These experiences are mirrored
in other diseases where medical advances have improved survival such
as AIDs and cystic fibrosis. With breast cancer the public have instilled
expectations that also fuel some of the challenges for both the long term
survivors and those with less good outcomes.
[1] Thorne et al. Qualitative Health Research 2013;23:863-875
IN06
LIVING ON BORROWED TIME: LONG TERM RESPONDERS
Shirley A. Mertz
Metastatic Breast Cancer Network, NewYork, NY, USA
A distinct benefit and result of targeted therapies for the management
of HER2 positive metastatic breast cancer is the growing number of
patients who are living longer with metastatic breast cancer. Few
such patients would call themselves “survivors,” since the disease is
S23
incurable. More accurately, they are Long Term Responders, who live as
fully as possible on borrowed time.
While I have lived with metastatic breast cancer for twelve years and
still undergo treatment, I can report that Long Term Responders are
acutely aware that metastatic cancer can progress at any time and at
any site in our body. Targeted treatments that have little toxicity enable
us to have a relatively high quality of life. As we interact with others,
we must contend with ignorance and misunderstandings about early
and metastatic breast cancer among extended family members, friends,
work colleagues, and the public. Such perceptions need to be addressed
through education and awareness by all global stakeholders in the
breast cancer community.
In addition, some healthcare providers believe that patients who have
had a long term response to treatment have resolved the psychological
and social issues strongly associated with those new to a metastatic
diagnosis—anxiety, depression, sleep disorders and access to social
support. To the contrary, such issues remain part of the continuum in
the journey with metastatic breast cancer. Long Term Responders often
must be proactive in seeking help to address these issues with their
healthcare providers, and some must seek help on their own.
Finally, Long Term Responders with the HER2 positive disease have seen
the approval of new therapies for the disease in the second and third lines
of treatment. These new treatments and a new era of precision medicine
provide hope to HER2 positive metastatic patients that, upon progression
of their disease, there will be other viable treatment options to consider.
While these developments are occurring, Long Term Responders are
aware that discussions have begun within the medical community and
among policy makers about whether the high cost of cancer treatments
in the second and third line make their future use sustainable by society.
Missing thus far is a discussion that includes the voice of Long Term
Responders from all metastatic cancers and the relative costs to society
when the lives of people who have responsibilities to others are cut
short. Some argue that in societies where the costs of cancer treatments
can no longer be justified, expensive treatments still will be available
to those who can afford them. With that outcome, the number of Long
Term Responders, made possible by the dedication, intelligence and
talents of scientists, researchers and clinicians, will no doubt decline.
IN07
NEW DRUGS, NEW SIDE EFFECTS: ENDOCRINE SIDE EFFECTS
Alexandru Eniu
Cancer Institute “I. Chiricuta”, Department of Breast Tumors, Cluj-Napoca,
Romania
Several targeted therapies with novel mechanisms of action have been
developed for use in advanced breast cancer. These new agents are
characterised by mechanism-based new side effects that can affect more
than one organ system. Moreover, the usual continuous administration
of these agents make them prone to generate cumulative toxicities over
time; therefore, the clinician has to be aware and recognize early signs
of subacute toxicities in order to proactively manage them. The purpose
of this presentation is to review the available evidence regarding the
endocrine effects of new, targeted agents, and to provide the clinician with
usable information to recognize, assess and manage these new toxicities.
Everolimus is the first mTOR inhibitor approved, in combination with
exemestane, for the treatment of hormone receptor positive advanced
breast cancer pretreated with a nonsteroidal aromatase inhibitor. One
of its effectors, mTORC1, functions as an integrator for four major
regulatory inputs: nutrients, energy, growth factors and stress. It also
controls the activity of several transcription factors implicated in lipid
synthesis and mitochondrial metabolism. Therapeutic mTOR inhibition
can lead in the clinic to hyperglycemia, hypercholesterolemia, and
hypertriglyceridemia. This is a common effect caused also by another
class of agents in clinical development, namely the PI3K inhibitors.
Hyperglycemia and hyperlipidemia are anticipated class effects of agents
affecting the PI3K/AKT/mTOR pathway as this pathway mediates signals
downstream of the insulin receptor. The management of these toxicities
mandates to check glucose and lipids level before and during treatment.
S24
Abstracts / The Breast 24 S3 (2015) S21–S75
The majority of patients will develop only grade 1-2 alterations.
Hyperglycemia should be adequately treated as per diabetes mellitus
recommendations. Hyperlypidemia should also be treated according
to current guidelines; for triglicerid levels above 500 mg/dl, the use
of lipid-lowering therapies, such as fibrates or HMG CoA reductase
inhibitors are indicated to avoid pancreatitis arising from extremely
high levels of triglycerides or cholesterol, based on extrapolation of data
from cardiovascular diseases. Data on other, less frequent endocrine
toxicities will also be reviewed in the presentation.
IN08
TREATMENT ASSOCIATED RISKS: IDENTIFYING AND TREATING
PULMONARY TOXICITY
Hope S. Rugo
University of California San Francisco, Breast Oncology Clinical Trials
Education, San Francisco, USA
The treatment of metastatic breast cancer includes a variety of
therapeutic modalities, including hormone therapy, chemotherapy
and radiation. Newer targeted have improved progression free survival
and response to hormone therapy for patients with hormone receptor
positive disease. The benefit of therapy must be weighed against
potential toxicity, and it is critically important that serious risks are
well recognized. Clinicians must both inform patients about risk, and be
familiar with early signs of toxicity as well as appropriate interventions.
Clearly both radiation and chemotherapy can cause pulmonary toxicity,
with prior radiation increasing the risk of inflammation from specific
agents such as taxanes. Inflammation of the lungs is referred to as noninfectious pneumonitis, or NIP, and is generally a diagnosis of exclusion.
Two new classes of targeted agents have been approved in combination
with hormone therapy for the treatment of metastatic, hormone
receptor positive breast cancer. Everolimus, an mTOR inhibitor, is the
first of the class of drugs active within the PI3K pathway to be approved
in combination with exemestane after progression of disease following
treatment with nonsteroidal aromatase inhibitors [1]. The most common
toxicities from everolimus include stomatitis, fatigue, hyperglycemia,
and NIP; these class effects are seen across indicated diseases [2].
NIP associated with everolimus is rare, with > grade 3 NIP observed in
3% of patients enrolled in the phase III Bolero II trial. No known risk
factors have been identified that increase the risk of NIP. The majority
of NIP occurs in the first 6 months of treatment, and is associated with a
risk of treatment discontinuation [3].
Generally grade 1 NIP can be monitored without specific intervention,
and is defined as radiographic findings without symptoms. Classic
radiographic findings include ground glass opacities, or patchy or diffuse
airway consolidation. Grade 2 NIP also includes cough and shortness of
breath without hypoxia. Treatment includes holding everolimus until
recovery of symptoms to grade 1 or less; drug should be restarted
as tolerated at a reduced dose. Corticosteroids may be considered
depending on the severity of symptoms. Patients whose symptoms do not
recover within 4 weeks should discontinue therapy. Symptoms of grade
3 NIP includes shortness of breath, hypoxia requiring supplementary
oxygen and occasionally fevers, again with classic radiographic findings.
Everolimus must be held and treatment with corticosteroids should be
instituted. In most cases, rechallenge with everolimus is not advised.
The differential diagnosis of NIP includes infection, progression of
malignant disease, and toxicity from other therapies. Consultation with
a pulmonary specialist and/or additional diagnostic procedures should
be considered. Treatment with antibiotics should be considered if
infection cannot be ruled out. Of patients in Bolero II with grade III NIP
or related pulmonary events, 75% had resolution of symptoms to grade
1 or less by 5.4 weeks [4].
Early identification and appropriate treatment of symptomatic NIP is
necessary in order to avoid more serious clinical effects; both physicians
and patients should be aware of symptoms. Baseline radiographic
studies should be obtained, and prompt evaluation and treatment is
indicated for any respiratory complaints.
The toxicity profile of PI3K inhibitors appears to differ from that
seen with mTOR inhibitors, with PI3K side effects including rash and
hyperglycemia [5]. The second class of approved agents includes
palbociciclib, a cyclin dependent kinase 3/4 inhibitor with a unique
toxicity profile primarily including reversible neutropenia [6]. Given
these non-overlapping toxicities, alternate targeted therapies could be
employed in patients with a previous diagnosis of NIP.
[1] Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal
hormone-receptor-positive advanced breast cancer. N Engl J Med.
2012;366:520-529.
[2] Rugo HS, Pritchard KI, Gnant M, et al. Incidence and time course of
everolimus-related adverse events in postmenopausal women with
hormone receptor-positive advanced breast cancer: insights from
BOLERO-2. Ann Oncol. 2014;25(4):808-815.
[3] Jerusalem G, Ellard S, Fasolo A, al. e. Non-infectious pneumonitis
(NIP) in breast cancer (BC) patients treated with everolimus
(Afinitor™) containing therapy: analysis of five studies. Cancer Res.
2009;69(24 suppl 3):Abstract 1115.
[4] Aapro M, Andre F, Blackwell K, et al. Adverse event management in
patients with advanced cancer receiving oral everolimus: focus on
breast cancer. Ann Oncol. 2014;25:763-773.
[5] Chia S, Gandhi S, Joy AA, et al. Novel agents and associated toxicities
of inhibitors of the pi3k/Akt/mtor pathway for the treatment of
breast cancer. Curr Oncol. 2015;22:33-48.
[6] Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6
inhibitor palbociclib in combination with letrozole versus letrozole
alone as first-line treatment of oestrogen receptor-positive,
HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a
randomised phase 2 study. Lancet. Oncology. 2015;16:25-35.
IN09
TOXICITY OF MODERN IMMUNOTHERAPY APPROACHES
Carlos H. Barrios
PUCRS School of Medicine, Porto Alegre, Brazil
New immunotherapy approaches are emerging as exciting alternatives
for the treatment of a variety of tumors. Better understanding (albeit
still incomplete) of the mechanisms involved in the interaction of the
immune system with cancer cells, particularly those involved with
the ability of tumors to escape immune surveillance, has led to the
development of new therapies with encouraging results.
While strictly still a targeted approach, the fact that the target in this
case is the host immune system, immunotherapy (sometimes with the
same drug) has resulted in responses across different tumors types.
As with every new therapy, issues related to toxicity and tolerability are
of particular importance if we are going to be able to translate all the
potential benefits of these new immune treatments to our patients.
While the experience in Breast Cancer remains preliminary, some of
these approaches have been already extensively tested in other tumor
types where toxicities have been described and different management
strategies have been proposed.
We need to recognize that while checkpoint inhibitors have taken most
of the press so far, cancer immunotherapy involves a number of other
immune based strategies among which: cytokines, cancer vaccines and
adoptive cell therapy.
It is essential for the practicing oncologist to familiarize with the
diagnosis and management of the toxicities associated with these
different ways of interfering with the immune response in our patients.
In this regard, the first and unavoidable concept to address is that these
adverse events are different from those we are used to encounter with
chemotherapy and other targeted approaches.
The underlying mechanism responsible for the toxic effects seems
to be a hyperactivated T-cell response redirected against normal
tissues. Unfortunately, the therapeutic response we try to induce
is not restricted enough to tumor cells and leads to off-target effects
generating an immune response that cross-reacts with normal tissues
causing autoimmune organ damage. Checkpoint inhibition and adoptive
cell therapy both lead to the expansion of a limited population of
Abstracts / The Breast 24 S3 (2015) S21–S75
immune cells with more specific set of autoimmune effects. Cytokines
on the other hand, seem to generate a more global and non-specific
T-cell response.
Due to the central role of the immune system it would be expected
that many different organ systems could be affected leading to diverse
adverse events, however, some organs seem to be more frequently
involved than others. Skin, GI tract, liver and endocrine glands are the
main sites of autoimmune toxicity with these therapies. Nervous system,
lungs and kidneys can also be involved but generally less frequently so.
Very pertinent to this discussion, the duration of some of these
therapeutic responses seem to be rather long raising issues of potential
long term effects yet to be clearly described and studied.
[1] Weber JS, Yang JC, Atkins MB, Disis ML. Toxicities of Immunotherapy
for the Practitioner. J Clin Oncol 2015; 33: 1-8.
[2] Gangadhar TC, Vonderheide RH. Mitigating the toxic effects of
anticancer immunotherapy. Nat Rev Clin Oncol 2014; 11(2): 91–99.
IN10
THE ROLE OF PATIENT REPORTED OUTCOMES
Lesley Fallowfield,
Brighton & Sussex Medical School, University of Sussex, Sussex Health
Outcomes Research & Education in Cancer, Falmer, UK
Patient Reported Outcomes (PROs) are any data that comes directly
from the patient without the intervention of a healthcare professional
or other patient proxy. PRO measures can include interviews conducted
for example in patient preference studies and standardised, validated
health-related quality of life questionnaires available for completion
electronically or on paper. The later tend to be employed in clinical
trials. It has been assumed that the recording of Adverse Events by
clinicians reliably documents patients’ side-effects and symptoms of
disease and treatment. Unfortunately a large accumulating body of
evidence suggests that the frequency and severity of many symptoms
that impact upon an individual patient’s quality of life go underreported, under-recognised and consequently under-treated. This is
unacceptable as the aim of any treatment in MBC is palliation and also
potentially dangerous from a drug safety point of view. The inability of
traditional methods for capturing AEs has led to renewed interest in
incorporating PROs with CTC-AEs in clinical trials and utilising PROs
outside a clinical trial setting, to monitor more accurately the harms and
benefits that patients experience. Many standardised, well validated
instruments or PRO measures are available with translations into most
languages. Most frequently used are the generic FACT (http://www.
facit.org/FACITOrg/Questionnaires) and EORTC-QLQ-C30 http://eortc.
be) questionnaires. Both have breast cancer specific modules/subscales
and the FACT in particular has several other specific subscales covering
for example treatment with EGfR inhibitors, taxanes, anti-angiogenisis,
endocrine and monoclonal antibodies. Recently the FDA and EMA have
published guidance for industry on how to utilise PROs in applications
for drug labelling claims. There has also been an important initiative,
funded by the NCI, to produce a Patient-Reported Outcomes version of
the Common Terminology Criteria for Adverse Events (PRO-CTCAE), and
which is suggested for use in NCI sponsored trials. (http://outcomes.
cancer.gov/tools/pro-ctcae.html). There is evidence from many tumour
sites that PROs are good prognostic and predictive indicators increasing
their utility by helping to demonstrate which patients are benefitting
from treatment and those for whom it is futile.
IN12
THE ROLE OF CDK AND PI3K/MTOR INHIBITORS
Fabrice André
Gustave Roussy Cancer Center, Villejuif, France
Analyses from TCGA project have shown that, beside ER, there are three
pathways activated in breast cancer namely PI3K/mTOR, CDK4, p53.
S25
These pathways can be activated by a genomic-dependant (mutation /
gene amplification) or independent mechanism. PI3K/mTOR and CDK4
have also been reported to be involved in the resistance to endocrine
therapy. All these data have led to the concept that PI3K, mTOR or CDK4
inhibition could reverse or delay resistance to endocrine therapy.
Everolimus is a mTOR inhibitor. Three randomized studies, including
one phase III, have shown that everolimus improves patient outcome
when added to endocrine therapy. This drug is now approved in patients
who present a resistance to non-steroidal aromatase inhibitors. There
are several efforts to better define the subset of patients who derive
large benefit from everolimus. Next generation sequencing analyses
have suggested that having multiple genomic alterations could be
associated with lower sensitivity to the drug. Molecular analyses from
phase II studies have suggested that mTOR activation could predict
higher sensitivity to the drug.
PI3K activated AKT1 by generating PI3P. At the opposite, PTEN
decreases this rate of PI3P and therefore inhibit signal transduction.
Activating mutations of PIK3CA occur in 25% of ER+ breast cancer. PI3K
inhibitors include non-selective PI3K inhibitors and alpha-selective
PI3K inhibitors. Alpha-selective PI3K inhibitors are expected to present
a higher bioactivity on the alpha isoform of PI3K and should present
higher activity in patients presenting PIK3CA mutant ER+ BC. Phase III
trials are ongoing to evaluate the efficacy of PI3K inhibitors
CDK4 is a kinase activated by Cyclin D1 and that phosphorylates Rb. Two
randomized trials, including one phase III registration trial, have shown
that adding CDK4 inhibitor (palbociclib) to endocrine therapy improves
outcome. There is no evidence until now that CCND1 amplification
could predict benefit of CDK4 inhibitors. Beyond palbociclib, two other
CDK4 inhibitors (abemaciclib and LEE011) are being evaluated in phase
III trials in metastatic breast cancers. Ongoing trials in the preoperative
setting will generate hypotheses about predictive biomarkers.
Overall, two targeted therapies have been shown to improve outcome in
patients with ER+ mBC. The future will consist in better positioning each
of these drugs, improving guidelines for management, and will finally
aim to combine drugs targeting ER, CDK4, PI3K/mTOR inhibitors.
IN13
REVOLUTIONIZING ER+ ABC MANAGEMENT: ESR1 AND OTHER
SUSPECTS IN RESISTANCE
Véronique Diéras
Institut Curie, Department of Medical Oncology, Paris France
About 70% of all BC express estrogen receptor  (ER), the product of ESR1
gene. Endocrine therapies (ET) represents the main treatment for these
subtypes and includes selective estrogen modulation (SERM), aromatase
inhibition (AI) and selective estrogen receptor downregulation (SERD).
However, the majority of ABC patients will develop resistance, leading
to disease progression. Significant strides have been made in the
understanding of the mechanisms of resistance to ET leading to several
targeted approaches as inhibitors of PI3K/mTOR pathway and cyclindependant kinase 4/6.
The implementation of molecular screening and next generation
sequencing (NGS) of primary and metastatic breast cohorts provided a
lot of genetic data as amplifications and/or mutations in a small subset
of tumors.
Recently, studies have identified mutations of ESR1 as an important
mechanism of acquired resistance to AI therapy. These mutations
are very rare in primary tumors and occur in 15-25% in metastatic
disease with a correlation between the number of prior ET and the
mutation frequency. These mutations in the ligand-binding site result
in constitutive activation of ER in the absence of estrogen binding. In
in vitro studies, tumor cells with mutations of ligand binding domain
exhibit responsiveness to antiestrogen therapy but a higher drug
concentration is required. New agents as SERD are in clinical trials with
the hypothesis to be more selective in ESR1 mutated tumors.
Less common but interesting are mutations of HER2 identified in a
small subset of breast cancers without HER2 amplification. The in vitro
studies shown that most commons mutations were activating mutations
S26
Abstracts / The Breast 24 S3 (2015) S21–S75
and confer sensibility to neratinib, an irreversible HER tyrosine kinase
inhibitor while lapatinib was not active. Currently a clinical trial is
examining the activity of neratinib in patients with HER2 mutated
breast cancer.
Targeting the fibroblast growth pathway appear to be relevant as
FGFR1 amplification occurs in 10% of all breast cancers, and enriched
in luminal B subtype and associated with resistance to ET. Clinical trials
have explored the potential to target FGFR signalling in breast cancer
with multitargeting inhibitors as dovitinib and lucitanib, and further
studies with other agents and in combination with endocrine therapy
are ongoing.
Other rare genetic events can been found also in breast cancer such
as mutation/amplification KIT, MET, PDGFRA and may represent
therapeutic target. Due to the very low frequency of such molecular
alterations, it is important to consider a new approach for clinical trials
as AURORA or SAFIR02 programs.
ER signalling remains an important therapeutic target even in the
resistance setting. These new data in molecular characterization provide
strong rational for new strategies to either manage or impede resistance
to ET. In addition, there is a need for biologically driven criteria to
guide treatment choice, identification of the optimal combinations or
sequences of targeted agents and integration of new agents into current
regimens.
[1] Cancer Genome Atlas Network. Comprehensive molecular portraits
of human breast tumours. Nature 2012; 490:61-70.
[2] Goncalves R, Warner WA, Luo J and Ellis MJ New concepts in breast
genomics and genetics. Breast Cancer Research 2014, 16:460.
[3] Segal CV, Dowsett M Estrogen receptor mutations in Breast cancer –
New focus on an old target. Clin Cancer Res 2014, 20(7) 1724-26.
[4] Zardavas D, Maetens M, Irrthum A et al: The AURORA initiative for
metastatic breast cancer BJC (2014) 111, 1881-87
IN14
IS OVARIAN ABLATION MANDATORY IN PRE-MENOPAUSAL ER+ ABC
PATIENTS?
Jonas Bergh
Karolinska Oncology, Radiumhemmet, Cancer Centre Karolinska,
Karolinska Institutet and Univeristy Hospital, Stockholm, Sweden
Present consensus: “For premenopausal women, ovarian suppression/
ablation combined with additional ET is the first choice.” The formal
evidence for this seems limited; six prospective and randomized
studies were published in the -80- and -90 ties with a total patient
number 741 randomized individuals. Four of these studies failed to
demonstrate any difference between oophorectomy and “tamoxifen”,
while the largest study with 318 patients demonstrated an improved
progression free survival, while the sixth study with 171 randomized
patients demonstrated a survival gain for the combination of buserelin
and tamoxifen vs. tamoxifen or buserelin alone.
For the present question we lack studies with sufficient power, therefore
we need to extrapolate from the adjuvant situation.
Data from more recent and large adjuvant studies (TEXT/SOFT) has
demonstrated a gain by the combination of buserelin for five years
and examestane in younger patients, still menstruating after adjuvant
chemotherapy compared with tamoxifen alone.
One can also note the EBCTCG data from 100.000 patients demonstrated
that the relative effect by chemotherapy was similar, irrespective of age
and tamoxifen use.
Despite the lack of similar prospective data from the metastatic
situation it would likely be a better option to offer an LHRH agonist
(oophorectomy) combined with an aromatase inhibitor instead of
tamoxifen alone as the first choice for a premenopausal patient with an
ER positive relapse.
Complicating factors: The immune expression of ER is not infrequently
heterogeneous in primary breast cancers. Some studies have
demonstrated that that adjuvant therapies may drive clonal selections of
cells not expressing the therapy predictive drug target, i.e. Her-2 and ER,
resulting in the “loss” of ER in 1/6 to 1/3 patients in the corresponding
metastatic lesion. More recent data from metastatic biopsies has
revealed that mutations may occur in the ER ligand-binding domain
causing, implicating resistance to conventional endocrine therapy.
The choices of therapy in the metastatic setting for a premenopausal
patient should be influenced by; relapse on adjuvant endocrine therapy
together site of recurrence, performance status and laboratory findings.
In some situations up front chemotherapy is the preferred strategy;
patients having a rapid relapse on optimal adjuvant endocrine therapy,
in particular if previously not treated with chemotherapy. Furthermore
one should also discuss to use chemotherapy if a metastatic biopsy
reveals “Luminal B like features”. While loss of ovarian function has
added value as described above, one should of course consider to use
chemotherapies with a higher likelihood to induce amenorrhea, thereby
having dual functions.
Conclusions: The evidence for some of the discussed strategies is low. In
some premenopausal patients the first preferred management strategy
should include ovarian ablation, while other up-front therapy options
should be discussed, in particular when there is a substantial risk for
“endocrine resistance”.
IN15
OPTIMAL MANAGEMENT OF TRIPLE NEGATIVE METASTATIC BREAST
CANCER (TODAY)
Lisa A. Carey
Lineberger Comprehensive Cancer Center, University of North, Dept. of
Medicine, Chapel Hill, USA
Conventional treatment for metastatic TNBC centers on cytotoxic
chemotherapy. Polychemotherapy is generally reserved for symptomatic
or rapid visceral progression, and sequential single agents for the rest.
The TNBC subset within randomized phase III studies suggests that
weekly paclitaxel is superior to microtubule-directed agents nabpaclitaxel or ixabepilone in the first-line setting [1] and that eribulin
is at least equal to capecitabine in later line settings [2]. Given the
association of TNBC with molecular subtypes that have aberrant
DNA damage response, trials have examined the role of direct DNAdamaging agents, such as platinum drugs, and targeting DNA damage
response with PARP inhibitors in TNBC. The recently reported TNT trial
found equivalence of carboplatin and docetaxel in first-line therapy
of metastatic TNBC, however within those tumors known to be BRCAassociated, the platinum outperformed the taxane, and within the
minority of TNBC that are not of the basal-like molecular subtype,
the taxane appeared to outperform the platinum [3]. These findings
suggest mechanisms for tailoring therapy in both the metastatic and
nonmetastatic settings. However, the TNT trial included a planned
crossover; and there was no difference in overall survival, suggesting
that while disease control initially may be facilitated by these selection
strategies, at this time there is no effect on survival if all drugs are
available. Given the palliative nature of treatment of metastatic disease
and the highly variable toxicity profiles of all these drugs, decisionmaking may reasonably be made on the basis of toxicity, schedule and
personal preference.
TNBC molecular heterogeneity has stymied efforts to develop targeted
therapy. Promising approaches that have not developed into successful
treatment include antiangiogenic drugs such as bevacizumab [4], EGFR
inhibitors [5,6], and PARP inhibition outside of those patients with
germline BRCA1/2 mutations [7], although there is clearly activity of
these drugs in BRCA-associated tumors. At AACR 2015, intriguing data
from a pembrolizumab phase I study suggest that immune checkpoint
targeting may be the next exciting direction in TNBC [8].
[1] Rugo H et al. CALGB 40502/NCCTG N063H: Randomized phase III
trial of weekly paclitaxel (P) compared to weekly nanoparticle
albumin bound nab-paclitaxel (NP) or ixabepilone (Ix) with or
without bevacizumab (B) as first-line therapy for locally recurrent
or metastatic breast cancer (MBC). J Clin Oncol 30, 2012 (suppl;
abstr CRA1002).
[2] Kaufman P et al. A Phase III, Open-Label, Randomized, Multicenter
Study Of Eribulin Mesylate Versus Capecitabine In Patients With
Abstracts / The Breast 24 S3 (2015) S21–S75
Locally Advanced Or Metastatic Breast Cancer Previously Treated
With Anthracyclines And Taxanes. 2012 CTRC-AACR San Antonio
Breast Cancer Symposium.
Tutt A et al. TNT: A randomized phase III trial of carboplatin
compared with docetaxel for patients with metastatic or recurrent
locally advanced triple negative or BRCA1/2 breast cancer. 2014
CTRC-AACR San Antonio Breast Cancer Symposium. Abstract S3-01
O’Shaughnessy J et al. A meta-analysis of overall survival data
from three randomized trials of bevacizumab (BV) and first-line
chemotherapy as treatment for patients with metastatic breast
cancer (MBC). J Clin Oncol 28:15s, 2010 (suppl; abstr 1005).
Carey LA et al. TBCRC 001: randomized phase II study of cetuximab
in combination with carboplatin in stage IV triple-negative breast
cancer. J Clin Oncol. 2012 Jul 20;30(21):2615-23
Baselga J et al. Cetuximab + Cisplatin in Estrogen Receptor-Negative,
Progesterone Receptor-Negative, HER2-Negative (Triple-Negative)
Metastatic Breast Cancer: Results of the Randomized Phase II BALI1 Trial. Cancer Research: December 15, 2010; Volume 70, Issue 24,
Supplement 2.
Gelmon KA et al. Olaparib in patients with recurrent high-grade
serous or poorly differentiated ovarian carcinoma or triple-negative
breast cancer: a phase 2, multicentre, open-label, non-randomised
study. Lancet Oncol. 2011 Sep;12(9):852-61
Emens L et al. Inhibition of PD-L1 by MPDL3280A leads to clinical
activity in patients with metastatic triple-negative breast cancer
(TNBC). AACR Annual Meeting; Philadelphia, PA. Abstract 6317
S27
CAN IMMUNE-BASED THERAPIES BE THE KEY?
consequence of constant immune selection pressure placed on genetically unstable tumor cells held in equilibrium, tumor cell variants
will be selected. They are no longer recognized by adaptive immunity
(antigen loss variants or tumors cells that develop defects in antigen
processing or presentation). They become insensitive to immune
effector mechanisms, or induce an immunosuppressive state within
the tumor microenvironment (tolerance). These tumor cells may then
enter the escape phase, in which their outgrowth is no longer blocked
by immunity. These tumor cells can re-emerge after adjuvant therapy
to cause metastatic disease. Is breast cancer immunogenic? Many data
suggest that it is. Many observations demonstrated the prognostic role
of TILs in TNBC breast cancer. TNBC are poorly differentiated tumor with
high genetic instability and very high heterogeneity. This heterogeneity
enhances the ”danger signals” and select clone variants that could be
more antigenic or, in other words, that could more strongly stimulate
a host immune antitumor response. Better prognosis in patients with
TN positive BC and higher TILs is also the result of an ”immunoediting”
process induced by chemotherapy. It has been evaluated in cellular and
animal models the emerging concept that the response to chemotherapy
is at least partly dependent on an immunological reaction against
those tumor cells that are dying during the chemotherapy. One of
the mechanisms whereby chemotherapy can stimulate the immune
system to recognize and destroy malignant cells is commonly known
as immunogenic cell death (ICD). Cancer cells succumbing to ICD are
de facto converted into an anticancer vaccine and as such elicit an
adaptive immune response. Which are the clinical implications of
all ”immunome” data produced in the last years? First, validation of
whether TILs are prognostic or predictive in HER2+ and TN breast cancer
is needed, preferably in a large population set with appropriate follow
up time. Second, validate immune genomic signatures that may be
predictive and prognostic in patients with triple negative disease. Third,
it will be essential to incorporate an ‘immunoscore’ into traditional
classification of breast cancer, thus providing an essential prognostic and
potentially predictive tool in the pathology report. Fourth, implement
clinical trials for TN breast cancer in the metastatic setting with drugs
that target immune-cell–intrinsic checkpoints. Blockade of one of these
checkpoints, cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) or
the programmed death 1 (PD-1) receptor may provide proof of concepts
for the activity of an immune-modulation approach in the treatment
of a breast cancer. We need also to better assess the role of TILs in DCIS
and to better explore the relationship between autoimmune disease
and cancer. The immune system remembers what it targets, so once the
system is correctly activated, it may mediate a durable tumor response.
[1] V. Shankaran, et al. IFN and lymphocytes prevent primary tumour
development and shape tumour immunogenicity. Nature 2001;410:1107.
[2] G. P. Dunn, A. T. Bruce, H. Ikeda, L. J. Old, R. D. Schreiber, Cancer
immunoediting: From immunosurveillance to tumor escape. Nat.
Immunol. 2002;3:991.
[3] Loi S, Sirtaine N, Piette F, et al. Prognostic and predictive value of
tumor-infiltrating lymphocytes in a phase III randomized adjuvant
breast cancer trial in node-positive breast cancer comparing the
addition of docetaxel to doxorubicin with doxorubicin-based
chemotherapy: BIG 02–98. J Clin Oncol 2013;31:860-867
[4] Dieci MV, Criscitiello C, Goubar A, et al. Prognostic value of
tumor-infiltrating lymphocytes on residual disease after primary
chemotherapy for triple-negative breast cancer: a retrospective
multicenter study. Ann Oncol. 2014;25:611-8.
[5] Zitvogel L, Kepp O, Kroemer G: Immune parameters affecting
the efficacy of chemotherapeutic regimens. Nat Rev Clin Oncol
2011;8:151-160
Giuseppe Curigliano
Istituto Europeo di Oncologia, Division of Experimental Cancer Medicine,
Milan, Italy
IN18
[3]
[4]
[5]
[6]
[7]
[8]
IN16
RESURRECTING PARP INHIBITION
Andrew Tutt
Kings College London, School of Medicine, Guy’s Hospital Cam,
Breakthrough Breast Cancer Research Centre, London, UK
The use of PARP inhibitors has been most discussed in the context of
their ability to induce synthetic lethality in BRCA1 and BRCA2 associated
malignancies. This has led to a licence for Olaparib in advanced BRCA1/2
associated ovarian cancer.
The role of PARP inhibitors in breast cancer is currently under
investigation with studies focussed on both metastatic and early forms
of BRCA1/BRCA2 associated breast cancer.
Early after proof of concept was shown in BRCA associated breast cancer
with potent PARP inhibitors the field became distracted by Phase 2
evidence of significant activity for the drug Iniparib in combination
with Gemcitabine and Carboplatin. This drug was found not to be
a PARP inhibitor neither to add significant benefit to platinum based
chemotherapy. Since then the role of PARP inbibitors in sporadic, non
BRCA, breast cancer has been little investigated.
I will review current Trials activity both in the BRCA mutation associated
and the BRCA ‘wild type’ breast cancer context and some putative
biomarkers suggested to be of relevance for patient selection in these
Trials. I will also discuss early phase data relating to other targeted
therapy in breast cancer in both BRCA mutated and sporadic contexts.
IN17
A fundamental ”dogma” of tumor immunology and of cancer immunosurveillance in particular is that cancer cells express antigens that
differentiate them from their non-transformed counterparts. Tumor
antigens are overexpressed normal proteins and therefore are subject
to immunological tolerance. Immune system controls not only tumor
”burden” (quantity) but also tumor ”quality” (immunogenicity). As a
TRIPLE NEGATIVE BREAST CANCER: THE ROLE OF ANDROGEN
RECEPTOR AND ITS INHIBITORS
Clifford A. Hudis, Tiffany Traina
Memorial Sloan Kettering Cancer Center, Breast Cancer Medicine Service,
New York, USA
S28
Abstracts / The Breast 24 S3 (2015) S21–S75
The availability of relatively non-toxic targeted therapies directed at the
estrogen receptor and HER2 has emphasized the more limited systemic
therapy options for patients with triple negative disease. Conventionally,
in both the adjuvant/neo-adjuvant or metastatic settings, such patients
are offered cytotoxic chemotherapy which, while effective in many
cases, is associated with some toxicities. The androgen receptor (AR) has
not been routinely considered in breast cancer although it was known to
be expressed in estrogen receptor positive disease for several decades. In
exploratory work, several groups identified AR positive triple negative
tumors through parallel exploratory efforts utilizing gene expression
profiling. Preclinical models confirmed that AR can drive tumor growth
when exposed to androgens and that anti-androgens could then be
inhibitory. Based on this work a translational study was conducted
through the TBCRC that established activity for bicalutamide, a nonsteroidal androgen receptor inhibitor with long-established efficacy
in prostate cancer, in patients with hormone-receptor negative (and
almost universally HER2 negative) metastatic breast cancer. Several
questions are raised by this positive result:
1. Are there more effective agents? Current candidates could include
the 17 -hydroxylase/C17,20 lyase (CYP17A1) inhibitor, Abiraterone
or the androgen receptor antagonist enzalutamide (formerly
MDV3100) as each of these is effective in prostate cancer.
2. Is the selection of AR-positive patients optimized using current
techniques? The TBCRC study utilized DAKO IHC but cut-points,
alternative IHC antibodies, and gene expression profiling may yield
more sensitive and/or larger treatable cohorts.
3. Is randomized evidence of efficacy required for a relatively
uncommon cohort using palliative agents with markedly different
toxicity profiles as compared to “standard” chemotherapy?
4. Can adjuvant development proceed?
This lecture will address these questions with updated data.
IN19
IMAGING RECEPTOR EXPRESSION AND GLYCOLYTIC ACTIVITY USING
PET-CT TO INDIVIDUALIZE TREATMENT IN METASTATIC HER2
POSITIVE BREAST CANCER (MBC)
P. Flamen, G. Gebhart
Institut Jules Bordet, Université Libre de Bruxelles (ULB) Dpt. Nuclear
Medicine, Bruxelles, Belgium
Molecular Imaging (MI) techniques using PET-CT in oncology might
become a major tool as predictive biomarkers in metastatic breast
cancer. One of the most appealing applications of MI is the imaging of
the expression and the bio-accessibility of the target of the drug. New
biologicals that are being introduced now in oncology are extremely
expensive, being often only effective in a small proportion of patients
expressing the drugs target, and are often associated with a considerable
toxicity which can significantly impaire quality of life. Using these drugs
in an unselected population will thus constitute a major burden on
health care cost. Better upfront selection of patients will be of crucial
importance in order to increase the cost-effectivity of these drugs. MI
techniques should primarily aim at (pre)identifying those patients in
whom the drug is very unlikely to have a positive impact on treatment
outcome. In those patients, early treatment discontinuation, or
adaptation (changing dosing or adding other drug in order to overcome
resistance) could lead to a better patient adapted treatment regimen
and might positively impact on patient outcome (which remains to be
proven).
Before starting therapy with anti-HER2 drugs (eg. trastuzumab) or
drug conjugates using HER2 as a vector of potent antimitotic drugs
(eg. TDM1), MI can assess the presence and accessibility of the drug’s
target (eg. HER2 receptor) through the administration of a radiotracer
targeting the target of the drug itself, or of the vector of the conjugated
drug, thereby non-invasively assessing the well known intra-individual
heterogeneity compared to the primary tumor site and also among the
different tumor sites themselves. Considering the HER2 receptor, a trial
on the use of Zr89-labeled trastuzumab (Zr-T) in patient with HER2-
positive metastatic breast cancer showed uptake heterogeneity in 45%
of the patients, and absence of any uptake in 16 % of the patients.
A multicenter study (Zephir) exploring the role of molecular imaging
to identifying patients with HER2 positive metastatic BC unlikely
to benefit from HER2 targeting drug conjugate (TDM1) is ongoing
(sponsor: Institut Bordet). The results of an interim analysis of
some of the secondary and exploratory endpoints of the trial were
recently presented at the 2014 ASCO meeting in Chicago and will be
discussed during the lecture. When combining Zr-T imaging with early
measurement of tumor response (FDG PET imaging of glycolysis after
one single cycle), on a patient-based analysis, high negative (86%) and
positive predictive values (100%) in terms of metabolic and structural
response were obtained.
IN20
TOWARDS IMPROVED DISEASE OUTCOME COMBINED WITH A
REDUCTION OF TOXICITY USING NEW RADIATION THERAPY
TECHNIQUES
Hanneke J.M. Meijer, Martina Kunze-Busch, Philip Poortmans
Radboud University Nijmegen Medical Center, Department of radiation
oncology, Nijmegen, the Netherlands
Radiation therapy (RT) plays an important role in the treatment of
advanced breast cancer. However, side effects might occur, including
fibrosis, reduced cosmetic results, cardiac and pulmonary toxicity, and
impaired shoulder function.
The advent of CT-based treatment planning has enabled the
determination of individualised target volumes. Recently, the European
SocieTy for Radiotherapy and Oncology (ESTRO) published guidelines
for target volume delineation of the breast, thoracic wall and regional
lymph nodes. These guidelines result in smaller and individualised
target volumes. In combination with conformal RT, this will decrease
the dose to the lungs, heart and shoulder joint.
While 3D conformal RT is routinely used, the homogeneity and
conformality of the dose distribution can be further improved by using
modern techniques including IMRT or VMAT. Several studies have
shown that this will lead to a decrease of side effects, and reduced dose
to the lungs and heart. However, in view of their higher complexity and
the delivery of a low dose of radiation outside of the target volumes, sole
use of these techniques should only be used in challenging cases where
dose constraints cannot be met with standard techniques, like in cases
of a complex anatomy.
Accurate and reproducible patient positioning and target volume
localisation are always necessary, especially when using more conformal
RT techniques. For treatment planning, the setting of dose and volume
constraints for the organs at risk is of utmost importance. These can
be used to balance target volume coverage against the risk for late side
effects.
An important heart-dose sparing technique is respiratory control, by
breathhold or gating. With these techniques, patients can be irradiated
during the inspiration phase of the breathing cycle only, when the heart
is being pushed back- and downwards, thereby moving the heart away
from the target volumes. This can be combined with highly conformal
irradiation techniques to further reduce heart dose. This has also been
shown feasible for locoregional irradiation.
In treatment plan comparison studies, protons have shown to further
reduce the dose to the organs at risk. However, proton therapy dose
delivery is highly sensitive to patient positioning, varying shape of the
breast and breathing motion. Therefore, results from real cases should
be awaited for before this complex and expensive technique should be
used for routine practice.
Hypofractionation has proven to be safe for early stage breast cancer.
Recently, reports are being published for postmastectomy and
locoregional hypofractionation, showing similar results compared to
conventional fractionation in terms of tumour control and toxicity.
Extra attention has to be paid to dose homogeneity when using
hypofractionation.
Abstracts / The Breast 24 S3 (2015) S21–S75
IN21
OPTIMAL MANAGEMENT OF FATIGUE
Fausto Roila
Medical Oncology, “S. Maria” Hospital, Terni, Italy
Cancer-related fatigue is one of the most frequent and distressing
symptom of the neoplastic patients. Until 40% of patients referred
fatigue at diagnosis, 80-90% during cancer therapies and 20-50% after
the end of cancer therapies. Practice guidelines suggest that all cancer
patients and survivors be screened for cancer-related fatigue.
Comorbidities that could contribute to fatigue should be treated (i.e.,
hypothyroidism, heart failure) as well as cancer and its complications
(anemia), psychological problems (anxiety, depression, insomnia) and
cancer symptoms (pain, dyspnea, anorexia-cachexia).
Pharmacological therapies have been evaluated in few randomized
clinical trials. Unfortunately, psychostimulants (methylphenidate,
dexanphetamine, modafinil), antidepressant (paroxetine), acetylcholinesterase inhibitors (donezepil), l-carnitine and coenzyme Q10 have
reported negative results, except in some subgroup of patients with
severe fatigue receiving methylphenidate and modafinil. On the contrary,
corticosteroids (dexamethasone 4 mg twice day) demonstrated superior
efficacy to the placebo in terminal cancer patients.
Non-pharmacological treatments can be recommended to the patients
suffering from cancer-related fatigue. Several meta-analyses, systematic
reviews, and randomized trials have demonstrated that initiating or
maintaining adequate levels of physical activity can reduce cancerrelated fatigue in post-treatment patient. Actively encourage all patients
to engage in moderate level of physical activity after cancer treatment
such as 150 minutes of moderate aerobic exercise (fast walking, cycling
, or swimming) per week with an additional two to three sessions for
week of strength training such as weight lifting unless contraindicated.
Psychosocial interventions such as cognitive behavioural therapy /
behavioural therapy, psychoeducational / educational therapies can also
reduce cancer-related fatigue.
Randomized trials showed that cancer-related fatigue could be reduced
also by mindfulness-based interventions, yoga and acupuncture. Other
interventions such as biofield therapies (touch therapy), massage, music
therapy, relaxation, reiki and quigong require more research especially
in the post-treatment period.
[1] Bower JE, Bak K, Berger A., et al Screening, assessment and
management of fatigue in adult survivors of cancer: an American
Society of Clinical Oncology clinical practice guideline adaptation. J
Clin Oncol 2014; 32: 1840-1850.
IN22
DYSPNEA: THE HARDEST SYMPTOM TO CONTROL?
Matti Aapro
Multidisciplinary Institue of Oncology, Clinique de Genolier, Breast Center,
Genolier, Switzerland
Shortness of breath, breathlessness or dyspnea (bad breathing), is a
most distressing symptom, often perceived as imminent death. It has
many causes, besides cancer related changes in oxygen supply. It can
be of cardiac origin, and congestive heart failure is not a rare event in
breast cancer patients. It can be related to asthmatic manifestations,
airway obstruction, chronic obstructive pulmonary disease, pleural
effusion or pulmonary embolism (often non diagnosed repeated small
emboli). Anemia has to be excluded, and patient anxiety (a cause also
of minor dyspnea) has to be discussed. While relatively easily treatable
causes are being excluded (and of course in all settings where a
relieving intervention can not be offfered) one has to think of symptom
relief. Symptoms due to respiratory secretions are alleviated with
anticholinergic drugs and mucolytics. Physical therapy and methods of
respiratory management are profitable in the treatment of respiratory
symptoms. Radiation therapy relieves cancer-induced hemoptysis,
cough, chest pain and obstructive dyspnea (when laser desobstruction
S29
is not feasible). The main approaches to pleural effusion are drainage of
the effusion (by thoracocentesis or with permanent pleural catheters)
and pleurodesis (obliteration of the pleural space by causing the visceral
and parietal pleura to adhere to each other). Guidelines for treatment
and prevention of subsequent pulmonary emboli are available. A recent
review paper indicates that non-pharmacological interventions include
walking aids, breathing training and, in chronic obstructive pulmonary
disease, pulmonary rehabilitation (Level 1 evidence). Regular, low
dose, sustained release oral morphine (Level 1 evidence) titrated to
effect (with regular aperients) is effective and safe. Oxygen therapy
for patients who are not hypoxaemic is no more effective than medical
air. If a therapeutic trial is indicated, any symptomatic benefit is likely
within the first 72 hours. A systematic review has also shown that
benzodiazepines might have a role which needs to be better determined.
[1] Ried M, Hofmann HS. The treatment of pleural carcinosis with
malignant pleural effusion. Dtsch Arztebl Int. 2013;110:313-8.
[2] Lehto J, Anttonen A, Sihvo E. [Treatment of dyspnea and other
respiratory symptoms in palliative care]. Duodecim. 2013;129:395402.
[3] Ben-Aharon I, Gafter-Gvili A, Leibovici L, Stemmer SM. Interventions
for alleviating cancer-related dyspnea: a systematic review and
meta-analysis. Acta Oncol. 2012;51:996-1008
[4] Wiseman R, Rowett D, Allcroft P, Abernethy A, Currow DC. Chronic
refractory dyspnoea—evidence based management. Aust Fam
Physician. 2013;42:137-40
[5] Frere C, Debourdeau P, Hij A, et al. Therapy for cancer-related
thromboembolism. Semin Oncol. 2014;41:319-38
[6] Uresandi F, Monreal M, García-Bragado F, et al . National Consensus
on the Diagnosis, Risk Stratification and Treatment of Patients with
Pulmonary Embolism. Arch Bronconeumol. 2013;49:534-47.
IN23
CIRCULATING TUMOR CELLS AND TUMOR DNA: ARE LIQUID BIOPSIES
A DREAM?
Jean-Yves Pierga1,2, Francois-Clement Bidard1
1
Institut Curie, Laboratory of Circulating Tumor Biomarkers, SIRIC and
Medical Oncology Department, Paris, France; 2Université Paris Descartes,
Paris, France
Since the first large study in 2004, the enumeration of circulating tumor
cells (CTC) has emerged as a promising biomarker in breast cancer.
Although there are numerous methods to detect CTC in the research
setting, there is only one test that has repeatedly demonstrated its
clinical validity (i.e. association with outcome) in breast cancer. This has
been confirmed recently in a large pooled analysis the clinical validity
of circulating tumor cells (CTC) as a dynamic prognostic biomarker
in 1,944 metastatic breast cancer patients [2]. Moreover, this study
demonstrated the superiority of CTC count over the serum markers CEA
and CA15-3. Current prospective large interventional studies have been
specifically designed to demonstrate the clinical utility of CTC detection
in breast cancer patient, either as a prognostic factor (“TREAT CTC”
NCT01548677 and “STIC CTC” NCT01710605), or as a tool to reassess
the tumor HER2 status (“DETECT III” NCT01619111 and “CirCe T-DM1”
NCT01975142). Recent negative results of the SWOG500 trial using CTC
as a dynamic prognostic tool still supported the clinical validity of the
test, but have postponed the use of this test in routine. The clinical data
are less numerous in early stages, but also validate the prognostic value
of CTC. Specific DNA fragments can be detected in the plasma, in general
after the genetic alterations harbored by the primary tumor and/or
its metastases have been characterized. The contribution of ctDNA
relative to the use of CTC must be evaluated in prospective studies in
particular for monitoring metastatic disease as a «liquid biopsy». Several
highly sensitive techniques, such as digital PCR have been used for the
purposes of finding a single ctDNA molecule within a large volume
of plasma sample. Recent studies has shown that ctDNA detection is
associated with tumor burden but its prognostic value is unclear [3].
Demonstration that the method can be used to take better care of
patients with MBC in a cost-effective manner awaits further studies.
S30
Abstracts / The Breast 24 S3 (2015) S21–S75
Next generation sequencing analysis of ctDNA in plasma could also
complement current invasive biopsy approaches to identify mutations
associated with acquired drug resistance in advanced disease.
[1] Bidard FC., et al Clinical validity of circulating tumour cells in
patients with metastatic breast cancer: a pooled analysis of
individual patient data. Lancet Oncol. 2014;14:1470-2045
[2] Bidard FC, et al. Clinical application of circulating tumor cells in
breast cancer: overview of the current interventional trials. Cancer
Metastasis Rev. 2013;32:179-88.
[3] Madic. J, et al, Circulating tumor DNA and circulating tumor cells
in metastatic triple negative breast cancer patients, Int J Cancer,
2015;136:2158-65
IN24
CLONAL EVOLUTION IN BREAST CANCER PATIENTS AND PATIENT
DERIVED XENOGRAFTS
Sam Aparicio
University of British Columbia and the BC Cancer Agency, Department of
Breast and Molecular Oncology, Vancouver, Canada
The notion that most cancers are ecosystems of evolving clones has
implications for biological understanding and clinical application.
The evolution of clonal composition has particular significance when
evidence of positive or negative selection can be associated with the
clonal genotype or epigenotype. Over the last 4 years next generation
sequencing of tumours and methods for single cell analysis have opened
up this approach for solid epithelial malignancies. I will discuss the
implications of clonal evolution for cancer medicine and biological
studies of cancer with reference to breast cancers. We have developed
informatics approaches to population level clonal analysis and extended
these to single cell measurements of genotypes. I shall discuss our more
recent data from single cell sequencing and clonal analysis applied to
clonal evolution of patient derived tumour xenografts, to illustrate
the impact of clonal evolution on biological studies of cancer in model
systems.
IN25
PATIENT XENOGRAFT MODELS: CAN AN "AVATAR" HELP?
Jens Hoffmann
EPO – Experimental Oncology & Pharmacology Berlin-Buch, Berlin,
Germany
Patient derived xenografts (PDX or Avatars) are preclinical models
for which clinical relevance has been described in many preclinical
experiments. Several drug sensitivity screenings revealed an individual
response to standard of care treatments comparable to historical data
from clinical trials. Recently, preclinical phase II studies with up to 100
PDX models have demonstrated a strong correlation between tumor
biology and treatment response.
Breast cancer has been the first tumor type where targeted therapies
with a corresponding biomarker have been successfully introduced
(antiestrogens and herceptin). Nevertheless, frequently observed
treatment resistance caused by inherent genetic and cellular
heterogeneity of advanced breast cancer calls for more intensified
efforts to individualize treatment.
The manifold available genetic tests for ER+ tumors are only of prognostic
value for early relapse to endocrine therapy or late recurrence. For
advanced breast cancer, a clinically useful drug-specific predictor for
treatment response still remains elusive.
As it is now generally accepted that tailored treatment approaches,
including specific schedules or combinations, can improve the
therapeutic outcome for target-specific compounds and chemotherapy,
breast cancer care needs, next to “established treatment guidelines”,
support from integrative translational research. The implementation
of such approaches, starting already during diagnosis and surgery can
help to establish a rationale for an individual treatment out from the
numerous possible options.
Drug response in clinical trials with advanced breast cancer patients
can frequently not be correlated with mutations, gene expression
or other molecular markers as tissue samples are hardly repeatedly
available. The development of personalized response predictors
therefore still depend on the availability of surrogate models like PDX.
Comprehensive studies that correlate pharmacodynamic data from PDX
with systematic molecular tumor tissue characterization have improved
our understanding of the disease and helped to design diagnostic
procedures allowing optimal therapy for individual patients. These
wet lab data together with molecular signatures are used for in silico
modeling to identify new predictors for tailored therapies.
While PDX have demonstrated their value for identification and validation
of predictive signatures, a benefit for individual treatment prediction
is currently under evaluation. A larger implementation of PDX studies
in personal therapy planning is still restricted by several factors – the
time for development of such models, high costs, and the limited take
rates which are especially for breast cancer still challenging. However
humanization of the mouse models is currently under evaluation to
improve take rates and help to overcome some of the limitations. As we
found that engraftment rates of PDX tumors were strongly correlated
with advanced stage of the patient tumor, these models could especially
be of value for improving and personalizing treatment of advanced
disease. Furthermore PDX provide an exceptionally broad basis for
translational research and the development of targeted therapies in the
future.
IN26
BIOPSY, REBIOPSY AND DEALING WITH DISCORDANT RESULTS IN ABC
Nadia Harbeck, Rachel Würstlein
University of Munich, Breast Center, Munich, Germany
Targeted therapeutics are standard options in metastatic breast cancer.
Changes in tumor biology (e.g., hormone receptor (HR) or HER2 status)
between primary tumor (PT) and metastatic tissue may therefore
substantially impact outcome and treatment choice following first
recurrence in breast cancer (BC). A biopsy of the metastatic site may
thus help to verify the diagnosis and re-assess ER, PR, and HER2. In the
retrospective WSG DETECT PRIMET quality assurance study (n=635,
11 centers) BC phenotype in tissue from PT, involved primary lymph
nodes (LN), and disease recurrence (DR) was compared. Tumor biology
of metastatic and primary tissue differed in a substantial fraction of
patients (HR: 19%; HER2: 22%, TN: 18%) and more than half of all switches
occurred already in LN. Status changes, particularly loss of HR+ status,
had significant prognostic impact. In the PRIMET collective, a switch in
HR or HER2 status (or both) occurred in about 38% of metastatic tissue
biopsies. In the literature, there are numerous retrospective reports of
discordance rates as high as 30-40%. In prospective series, these rates
seem to be somewhat lower leading to changes in treatment in about
15% of patients.
For the above reasons, ABC2 recommended that a biopsy (preferably
providing histology) of a metastatic lesion should be carried out, if
easily accessible, to confirm diagnosis particularly when metastasis
is diagnosed for the first time (Cardoso et al, 2014). Whether these
observed discordancies represent true biological properties of the tumor
or merely methodological inconsistencies can not be decided in all cases.
If the results of tumour biology in the metastatic lesion truly differ from
the primary tumour, it is currently unknown which result should be
used for treatment-decision making. Since a clinical trial addressing
this issue is difficult to undertake, ABC2 recommended considering
the use of targeted therapy (endocrine and/or anti-HER-2 therapy)
when receptors are positive in at least one biopsy, regardless of timing.
In particular, specific targeted agents such as T-DM1 in HER2-positive
disease, which do not require combination with standard chemoor endocrine therapy, need to be used carefully in case of discrepant
tumor biology and therapy response must be closely monitored. Data
is still lacking on differences in molecular alterations between primary
Abstracts / The Breast 24 S3 (2015) S21–S75
tumor and metastases in particular regarding their clinical relevance.
Thus, therapy trials in ABC need to collect tissue not just from primary
but also from metastatic lesions in order to help understand tumor
heterogeneity and its impact on response to targeted therapies. New
comprehensive programs such as AURORA (BIG) as a pan-European
program or PRAEGNANT (NCT02338167) in Germany will enhance our
molecular understanding of tumor progression. Yet, until clinical trials
incorporating molecular information derived from metastatic lesions
have rendered clinically relevant results, patient management will
depend on standard ER, PR, and HER2 derived from metastatic biopsies.
[1] Cardoso F., et al. ESO-ESMO 2nd international consensus guidelines
for advanced breast cancer (ABC2). Annals of Oncology 2014;00:1–
18.
IN27
ADVANCED BREAST CANCER: IS THERE AN OPTIMAL SEQUENCE OF
SYSTEMIC ANTICANCER AGENTS?
Prudence A. Francis
Peter MacCallum Cancer Centre, Division of Cancer Medicine, Melbourne,
Australia.
The sequence of systemic anticancer agents for patients with HER2
negative ABC should be tailored according to a variety of factors
including:
•
Presence (HR+) or absence of hormone receptors (ER, PR)
•
Presence of other potentially actionable targets identified through
additional testing (eg. androgen receptor, BRCA mutation, next
generation sequencing)
•
Patient hormone profile in HR+ (postmenopausal vs premenopausal
vs male)
•
Relevant clinical trial availability
•
Prior adjuvant treatments
•
Disease-free interval (DFI) and progression-free survival with prior
therapies
•
Health (physiologic age, comorbidities, organ function, performance
status)
•
Burden (volume and sites) of metastatic disease
•
Cancer therapies accessible to patient (available and affordable)
•
Patient preferences (eg. alopecia, oral vs intravenous, 3-weekly vs
weekly)
•
Difficulty attending treatment centre
•
Toxicity with prior agents
For a patient with advanced disease, selecting the optimal sequence of
anticancer agents is also a dynamic process which evolves over time, as
the above factors do not remain constant. Patients with HR+ advanced
disease may survive for more than a decade, with possible change in ER/
PR expression, in addition to changes in age, comorbidities, cumulative
toxicities, available therapies, and new information from clinical trials
during that time. Endocrine therapies are the preferred initial options
for HR+ advanced disease in the absence of a need for rapid tumour
response or primary endocrine resistance. Loss of hormone receptor
expression during progression may influence the number of sequential
endocrine therapies. Patients with HR+ tumours experiencing short DFI
and/or PFS on prior endocrine therapies may be less suited to receiving
sequential different endocrine agents, while those with a slower tempo
of disease under endocrine therapy maybe suitable for a sequence of
consecutive different endocrine agents, in addition to withdrawal of an
endocrine agent and/or oestrogen, as additional therapeutic manoeuvres.
Patients with a lower burden of disease or older physiologic age may
be considered for multiple lines of endocrine therapy before initiating
cytotoxic therapy, and may receive capecitabine as initial cytotoxic
agent, ahead of anthracycline and taxane therapy. For patients who
prioritize avoiding alopecia, treatment with agents such as liposomal
doxorubicin, vinorelbine, capecitabine, gemcitabine and metronomic
cyclophosphamide may be chosen before taxanes. Patients travelling
long distances to a treatment centre or for whom weekly attendance
is problematic, may prefer 3-weekly docetaxel to weekly paclitaxel.
Patients who cease taxane treatment due to symptomatic peripheral
S31
neuropathy, may better avoid receiving drugs that may exacerbate
neuropathy (i.e., eribulin or vinorelbine) as their next treatment, even
though these drugs might be utilized subsequently, when neuropathy
symptoms improve.
IN28
DURATION OF FIRST-LINE CHEMOTHERAPY IN METASTATIC BREAST
CANCER
Alessandra Gennari, Nicoletta Provinciali
E.O. Ospedali Galliera, Division of Medical Oncology, Genoa, Italy
The management of metastatic breast cancer is a major clinical challenge
for oncologists. Indeed, in spite of all of the available agents, this stage
of disease can rarely be cured. With respect to treatment choice, it can
be assumed that virtually all patients with metastatic disease sooner
or later will require chemotherapy. In particular, for patients with
hormone receptor-negative or endocrine-resistant disease, cytotoxic
chemotherapy is indicated. The selection of optimum chemotherapy
is influenced by the characteristics of patient and cancer as well as
by patient and clinician preferences. There is, however, substantial
controversy over how long chemotherapy should be extended, in the
absence of significant toxicity, after the achievement of disease control.
Over the past two decades, several clinical trials have addressed the issue
of optimal chemotherapy duration in metastatic breast cancer [Gligorov
et al. 2014, Young-Hyuck et al. 2012, Alba et al. 2010; Mayodromo et al.
2009; Gregory et al. 1997; Gennari et al. 2006; Nooji et al. 2003; French
Epirubicin Study Group, 2000; Falkson et al. 1998; Ejlertsen et al. 1993;
Muss et al. 1991; Harris et al. 1990; Coates et al. 1987].
The impact of extending the duration of chemotherapy beyond a fixed
number of cycles has recently been investigated in a systematic review
of these 13 randomized trials evaluating first-line chemotherapy in
patients with metastatic breast cancer [Gennari et al. 2011]. A recent
update of this metaanalysis, including also the most recent trials, indicate
that longer chemotherapy duration is associated with a significant
increase in overall survival, equivalent to approximately 4 months
(hazard ratio [HR] 0.88, 95% CI 0.81-0.96) and a significant prolongation
of progression-free survival (HR 0.65, 95% CI 0.6-0.7), compared with
shorter durations. By multivariate analysis, no difference in effects on
overall survival and progression-free survival among subgroups defined
by time of randomization, study design, number of chemotherapy cycles
in the control arm, or concomitant endocrine therapy was detected.
After these results, patients should be therefore informed that they
will likely get the best chance for an improved outcome with a longer
chemotherapy administration. This approach must however be weighed
against the detrimental effects of continuous chemotherapy delivery on
quality of life. In fact, the management of a patient with metastatic breast
cancer needs to be tailored on patient’s and cancer’s characteristics, but
cannot even ignore patient’s needs and desires.
[1] Gennari et al. Extending the duration of first-line chemotherapy in
metastatic breast cancer: a perspective review. Ther Adv Med Oncol
2011;3:229-32
[2] Gennari et al. Duration of chemotherapy for metastatic breast
cancer: a systematic review and meta-analysis of randomized
clinical trials. J Clin Oncol. 2011;29:2144-9
IN29
SURGERY OF THE PRIMARY TUMOUR: SHOULD THE
RECOMMENDATION BE CHANGED?
Maria-João Cardoso
Champalimaud Foundation, Breast Unit, Lisbon, Portugal
Five to 10% of Breast Cancer Patients in the United States and Western
Europe present with Stage IV disease at diagnosis. Only approximately
one fifth of these patients will be alive after five years, and a minority
(up to 5%) will be long term survivors.
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Abstracts / The Breast 24 S3 (2015) S21–S75
For patients presenting with metastatic breast cancer at diagnosis
systemic therapy is clearly the first choice but retrospective data from
the last ten years showed an important benefit in survival when removal
of the primary lesion with or without radiotherapy was added to an
effective systemic treatment.
In 2011 and 2013 the ABC1 and ABC2 guidelines stated that the value of
removal of the primary lesion in patients with the novo stage IV breast
cancer was currently unknown but it could be considered in selected cases
adding that surgery would only be helpful if clear margins were obtained
and the axilla was addressed as in patients with early stage disease.
In December 2013, however, the results of two of the prospective ongoing
randomized trials addressing the topic of surgery of the primary versus
no surgery in de novo stage IV breast cancer, the TATA Memorial and
the Turkish Federation Trials, were presented in San Antonio and both
showed no benefit in overall survival for those patients submitted to
removal of the primary lesion, except in selected cases of patients with
isolated bone metastases.
The results of these two trials questioned the assumption of previous
reviews and meta-analysis that resection of the primary tumour in stage
IV breast cancer confers an important survival advantage. The potential
bias in these retrospective analysis were attributed to young age, small
tumours and a low burden of disease (oligometastatic).
Until more data are available from other ongoing prospective
randomized trials, with an expected accrual of around 1000 patients,
surgery should be cautiously recommended for de novo stage IV breast
cancer particularly in the case of uncontrolled metastatic disease or
when the disease is controlled in all sites but the burden is very high
and no complications are expected from the primary location. Surgery
seems to be still an option to consider in the case of oligometastatic
disease when stage IV NED (non evidence of disease) can be achieved.
Also surgery can be considered, with a palliative intent, for patients
with controlled systemic disease but with a locally progressing lesion.
Patients should be fully informed that for the moment loco-regional
treatment of stage IV breast cancer lacks evidence of any survival
benefit and for that reason and outside a clinical trial the choice, in case
of loco-regional treatment, should be the most conservative option with
the least possible morbidity.
[1] Badwe R, Parmar V, Hawaldar R, et al. Surgical removal of primary
tumor and axillary lymph nodes in women with metastatic breast
cancer at first presentation: A randomized controlled trial. In:
SABCS: 2013; San Antonio; 2013.
[2] Cady B, Nathan NR, Michaelson JS, Golshan M, Smith BL: Matched
pair analyses of stage IV breast cancer with or without resection of
primary breast site. Ann Surg Oncol 2008;15:3384-3395.
[3] Cardoso F, Costa A, Norton L, Cameron D, Cufer T, Fallowfield
L, Francis P, Gligorov J, Kyriakides S, Lin N et al. 1st International
consensus guidelines for advanced breast cancer (ABC 1). Breast
2012;21:242-252.
[4] Cardoso F, Costa A, Norton L, Senkus E, Aapro M, Andre F, Barrios CH,
Bergh J, Biganzoli L, Blackwell KL et al: ESO-ESMO 2nd international
consensus guidelines for advanced breast cancer (ABC2). Breast
2014;23:489-502.
[5] Harris E, Barry M, Kell MR: Meta-analysis to determine if surgical
resection of the primary tumour in the setting of stage IV breast
cancer impacts on survival. Ann Surg Oncol 2013, 20(9):2828-2834.
[6] Patrick J, Khan SA: Surgical Management of De Novo Stage IV Breast
Cancer. J Natl Compr Canc Netw 2015;13:487-493.
[7] Petrelli F, Barni S: Surgery of primary tumors in stage IV breast
cancer: an updated meta-analysis of published studies with metaregression. Med Oncol 2012;29:3282-3290.
[8] Soran A, Ozmen V, Ozbas S, al e: Early follow-up of a randomized
trial evaluating resection of the primary breast tumor in women
presenting with the novo stage IV breast cancer: Turkish study
(protocol MF07-01). In: SABCS: 2013; San Antonio; 2013.
IN30
SURVIVORSHIP IN ABC: WHICH ARE THE MAIN ISSUES?
Olivia Pagani
Oncology Institute of Southern Switzerland (IOSI), Breast Unit, Bellinzona,
Switzerland
As the outcome of ABC has significantly improved over the last decades,
the complex needs of patients living with advanced breast cancer and
their caregivers should be addressed not only in terms of supportive
and palliative care but also of “survivorship” requirements. The
multidisciplinary approach of ABC should encompass early in the history
of the disease not only physical but also functional, social, psychological
and spiritual domains (Zimmermann 2014).
It is important to clearly define with patients and families the disease
context (“chronic” preferred to “incurable” disease), addressing
the concept of uncertainty and tailoring the treatment strategy
according to individual priorities and disease status (Silverman 2014).
Specific psycho-social needs of young and elderly patients should
also be recognized and supported, i.e. social security, job flexibility,
rehabilitation (including sexuality), home and children care.
[1] Zimmermann C, Swami N, Krzyzanowska M et al. Early palliative
care for patients with advanced cancer: a cluster-randomised
controlled trial. Lancet. 2014. doi: 10.1016/S0140-6736(13)62416-2
[2] Silverman R, Smith L, Sundar S. ‘Is it my last christmas dinner?’
survival of cancer patients having palliative chemotherapy during
christmas period. BMJ Support Palliat Care. 2014;4 Suppl 1:A56.
IN31
ADDRESSING THE EMOTIONAL NEEDS OF PATIENTS WITH ADVANCED
METASTATIC BREAST CANCER
Lillie D. Shockney
Johns Hopkins University, Breast Center, Baltimore, USA
Though the majority of individuals diagnosed with breast cancer
today will become long term survivors, there continues to be many
who will be forced to eventually succumb to their disease. From the
point of diagnosis the focus of their care is on treating the disease and
preserving hope. However at some point, preferably earlier than it
currently happens today, the future hopes of these patients, many being
young mothers, needs to be asked about and effectively addressed. She
deserves to experience a good death.
Johns Hopkins has been conducting retreats for patients dealing with
advanced metastatic breast cancer since 2007. These retreats (3 days
and 2 nights) are held semi-annually. One retreat is for couples and
the other for patients not in a relationship; they are accompanied by a
female caregiver. During this time frank and open discussion is fostered
to help patients and their loved ones express what their greatest fears
are of what likely lies ahead. From the identification of these fears,
solutions are created and implementation begun with the goal that the
patient will experience a good death when the time comes.
A short video has been created to depict the heart and soul of the content
of these retreats with examples of fulfilling hopes for these patients in
alternative ways after they are gone.
Patients and their loved ones arrive, having completed a survey that
measures their fearfulness of the future and leave post retreat feeling
more prepared and less fearful, having tools, resources and alternative
methods to reduce their fears, fulfil their hopes of the future, and
prepare their family for life without them physically present.
A program planning guide has been created to facilitate the development
and implementation of similar retreats to take place nationally and
internationally.
Since the inception of these retreats through the Johns Hopkins Breast
Center, similarly designed retreats for patients with advanced pancreatic
cancer, metastatic colorectal cancer, and metastatic ovarian cancer have
also been held annually beginning in 2012.
https://www.youtube.com/watch?v=Bg02G2a7uHo
Abstracts / The Breast 24 S3 (2015) S21–S75
IN32
LIVING WITH MBC IS LIKE WALKING ON A TIGHT ROPE, A BALANCING
ACT USING ALL RESOURCES, TO HOLD ON AND REACH THE OTHER
END
Evi Papadopoulos
Europa Donna Cyprus, Nicosia, Cyprus
Balance in the world of breast cancer metastasis for a woman who is
going through the experience of the recurring disease, is essential for
her survival. She must find the inner and outer resources to meet the
challenges of her situation, to regain control, to harness her fears, to
cope, to strive for normality and create stability and continuity.
Much depends on her ability to adjust to the new situation, to
communicate with doctors and medical carers, to understand her
disease and try and live with it. However not all people have the same
skills or education or even stamina to cope with the progressing disease
and the new reality with shorter life prospects. Not all patients have the
inner strength to rise above their reality and to create a liveable daily
life within the family, the community and the working environment. So
they become emotional exhausted.
Women with MBC have been neglected, their needs unrecognised,
keeping most of them in the shadows overcome by depression,
disappointment and anxiety. Many felt that the medical world has
written them off.
‘’As patients we need our medical carers to educate us and to empower
us, to make us understand, to make informed choices with them, to have
a positive outlook to our condition, sustaining therapies and side effects.
We interpret survival in many ways, striving to discover our options to
reduce our stress, to boost our moral, to care for our self image. Whether
practical or spiritual, support improves our attitude, our pain threshold
and the final outcome’’.
In a multidisciplinary context of a specialised Breast Unit, an MBC
woman of any age, needs to be cared for by the health professionals who
can understand her individual situation, age and specific needs at every
step of the way ahead. She needs to know that she is safe that she can be
offered the best treatment choices and trust that the doctors will work
with her in choosing and monitoring, her medication regime. Patient/
advocate groups can be beneficial for empowerment and practical
support.
Family concerns, financial, social and work matters but also social
perceptions and taboos can be a huge burden on the MBC woman
increasing the distress from her disease.
The health system and the accessibility to treatments may cause further
uncertainty losing the precious balance and leading the MBC woman to
isolate herself and finally give up.
Bringing out in the open, the special multifaceted needs of an MBC
patient is an effort to improve services for better survival.
IN33
S33
as a cross sectional example of high income settings and reflect on the
policy lessons for the major emerging economies in terms of delivering
affordable systems for breast cancer care, specifically focusing on India
as an example of a complex emerging middle income country.
[1] Fernandez-Luengo R, Leal J, Gray A, Sullivan R. Economic burden
of cancer across The European Union: a population-based cost
analysis. Lancet Oncology 2013;14:1165-1174.
[2] Pramesh CS, Badwe RA, Sullivan R, et al. Delivery of affordable and
equitable cancer care in India. Lancet Oncology 2014;15:223-233.
[3] Mallath MK, Taylor DG, Sullivan R, et al. Growing burden of
cancer in India: epidemiology and social context. Lancet Oncology
2014;15:205-212
IN34
BREAST CANCER CARE ACCESS AND AFFORDABILITY: ARE DRUGS THE
MAIN ISSUE IN EUROPE?
David Taylor
University College London, Pharmaceutical and Public Health Policy Dept.,
London, UK
This presentation begins with a brief overview of the changing disease
burden due to breast cancer in Europe, and the extent to which survival
improvements have been associated with an emergent pattern of
advanced disease management challenges occurring in excess of a
decade after the initial diagnosis. It then presents recent data on the
overall costs of cancer care and oncology medicines in Europe and
globally, and in particular those associated with breast cancer care and
the interventions (ranging from radiological therapies to social support)
required to extend and improve the lives of the individuals and families
it affects.
The main barriers to overcome in further improving outcomes
are discussed, including the costs associated with accessing new
(intellectual property protected) anti-cancer medicines. In the latter
context an analysis of conflicting public and patient interests relating to
drug pricing is offered. On the one hand patients and clinicians may well
wish to optimise their minimal cost present use. On the other there are
important benefits to be gained from providing appropriate economic
and wider social incentives for both public and private investment in
continuing therapeutic and service innovation.
Potential solutions to current drug and other treatment related access
and affordability problems are in conclusion critically considered. While
the overall costs of breast cancer care are now in the order of 0.5 per cent
of all health spending (ie 0.05% of GDP) in the average European nation
(of which total pharmaceutical product outlays presently account for
around 20 per cent – estimates to be confirmed), the benefits gained
from effective treatment and care are also considerable. From an
informed welfare policy perspective short term cost saving measures
should not be permitted to undermine the longer term achievement of
reduced suffering and loss of life caused by breast and other cancers.
THE COST OF BREAST CANCER: A GLOBAL PERSPECTIVE
IN35
Richard Sullivan
Institute of Cancer Policy, King’s College London, King’s Health Partners
Comprehensive Cancer Centre, Guy’s Hospital Campus, London, UK
Across the world breast cancer continues to have a major economic
cost to countries and families. In high income settings direct care
and informal costs have to be balanced with productivity losses due
to premature mortality and morbidity. High resolution studies of the
economic burden of breast cancer show a wide variation in health care
costs per incident case, with the majority of expenditure in in-patient
(surgical, pathology, radiotherapy) and medicine costs. The ability to
explore these costs in relation to progress in outcomes measured by
changes in mortality across Europe provides clear policy messages for
emerging economies as their burden of breast cancer begins to rise
with changing socio-demographics. In this lecture we will explore the
relationship between breast cancer care costs and outcomes using EU28
CAN WE REALLY APPLY INTERNATIONAL GUIDELINES IN LIMITED
RESOURCES COUNTRIES?
G.S. Bhattacharyya1, Hemant Malhotra2, K. Govindbabu3, A.A.B. Ranada4,
Purvish M. Parikh5
1
Fortis Hospital, Anandapur, Kolkata, India; 2SMS Medical College, Jaipur,
India; 3Kidwai Memorial Institute of Oncology, Bangalore, India; 4Deenanath
Mangeshkar Hospital, Pune, INDIA; 5Asian Institute of Oncology, Mumbai, India
The Universal Declaration of Human Right states that “everyone has
a right to standard of living for the health and well being of himself
and his family”. Cancer patients are not an exception. Inequalities in
health, is probably an excellent indicator, reflecting the inequalities
in society. More-so the mix of cancer that occurs around the world is
driven largely by environment, geography and standard of living. Cancer
S34
Abstracts / The Breast 24 S3 (2015) S21–S75
is often regarded differently, in different settings: preventable and often
curable in developed nations but as a painful death sentence in limited
resource countries. A close look at cancer incidence rates according to
socio-economic, racial and ethnic groups in 80% of the world population
living in developing countries, reveal significant differences; 80% all
cancers are in advanced stage and are not curable, and 26% are caused by
infectious disease. There is strong evidence that, patients from resource
limited countries probably have higher incidence and shorter survival
after diagnosis of cancer. In-fact 60% of all cancer patients are in limited
resource country, 72% of all deaths from cancer occur in developing
countries, and 77% of disability adjusted life years and 78% of years lost.
This is due to limited access to medical treatment, un-informed about
early detection, as well as the quality of available care. One of the reasons
of improved outcomes of care in developed world has been due to use
of evidence based clinical practice guidelines. In-fact the improvement
of outcome has been due to guidance based cancer care, early detection
and awareness with prevention. However the guidelines which have
been developed for developed countries are difficult to adopt in limited
resource countries. This is mainly because of
a) Absence of expertise
b) Weak infrastructure
c) Costs
d) Epidemiological transition and guidelines not integrated in them
e) Accessibility
f) Data generated is usually not from the region of application
Hence very often there is resistance of application. If we are to have an
internationally harmonized guideline, then these guidelines will have to
have the following characters of validity, reproducibility, cost effective,
representative / multi-disciplinary, unambiguous clinical applicability,
flexibility, clear, reviewable, amenable to clinical audit. These guidelines
should be resource stratified and must be integrable with the existing
public health guidelines of the country. The concept of “resource – level
appropriateness” recognises that effective intervention have progressed
in high income countries through more than one generation. In a situation
of insufficient healthcare infrastructure, uneducated public, not covered
(out of pocket payment), calls for explicit analysis of effectiveness
and cost of alternative approaches, which may help in preventing or
countering natural attractions to newest, high technology (and expensive
intervention); this thinking although intuitively simple, but filling in the
details require systemic analysis of varying complexities.
IN36
IS A TWO-SPEED (RICH VS POOR) ONCOLOGY INEVITABLE?
George W. Sledge
Stanford University, Stanford, USA
Healthcare disparities arguably represent the single greatest cause of
cancer mortality on a global basis. Surveys of world health routinely
suggest that large swaths of cancer patients die because of inadequate
access to appropriate and potentially curative therapy. These disparities
in turn reflect major differences in wealth between and within nationstates, and at a structural level, differences between healthcare systems
designed to support public health and those that are not. To what extent
are these disparities inevitable; i.e., a simple function of the relative
wealth of nations? Can we significantly reduce cancer death rates in the
absence of admittedly utopian prescriptions for redistribution of global
wealth? Breast cancer represents a valuable case study for the issue of
“Two-speed Oncology”.
Nursing and Advocacy
OR37
UNMET PSYCHOSOCIAL AND QUALITY OF LIFE NEEDS OF PATIENTS
LIVING WITH METASTATIC BREAST CANCER
Marc Hurlbert2,3, Musa Mayer1, Katherine Crawford3, Shirley Mertz4,
Virginia Knackmuhs4
1
AdvancedBC.org, Advocacy, New York, USA; 2Avon Foundation for Women,
Breast Cancer Crusade, New York, USA; 3Metastatic Breast Cancer Alliance,
Advocacy, New York, USA; 4Metastatic Breast Cancer Network, Programs,
New York, USA
MBC Alliance members (>30) work together to improve the lives of MBC
patients.
Objective: Review prior literature and patient survey reports related to
MBC patients’ QoL needs, and assess extent to which US organizations
are meeting them.
Methods: (1) Research findings of >150 published, peer-reviewed
research articles on advanced cancer patients’ needs, including
quantitative and qualitative studies of MBC patients and their families,
were summarized around the realities of living with MBC. (2) 13 surveys
of ~8,000 MBC patients were examined for common concerns. (3) Desk
research analysis of leading US nonprofits’ patient advocacy, research,
education and support (n=16); analysis of websites (n=24) and print
materials (n=27); interviews with leadership about services for patients
(n=16); and online survey of helplines (n=8).
Results: The extensive research base around MBC QoL issues was
summarized into 6 categories: psychosocial distress; emotional
support; information about the disease, its treatment, and resources;
communication and decision making about care; relief of physical
symptoms; and practical concerns. Sources of emotional support,
individual and group psychotherapy, and counseling, as well as
adequate information about the disease, its treatments, and methods
to alleviate symptoms and side effects have been shown to be useful
in helping patients cope with MBC. However, patients are typically not
well informed in areas required for decision making about their care,
and patient–clinician communication can be difficult. MBC symptoms
and side effects of continuous treatment - fatigue, sleeping difficulties,
and pain - and emotional distress interfere with daily life; supportive
and palliative care is often insufficient. Financial hardship is a fact of life.
Information and support services have a major role in improving QoL.
While the majority of the major US breast cancer advocate organizations
focus on meeting the support needs of the breast cancer community,
not enough attention is paid to the MBC patient population. Information
materials often require relatively high health literacy and knowledge of
how to search and evaluate materials found on the Internet. There are
limited dedicated helpline services for MBC patients; conferences/inperson networking events tend to be in large cities. Gaps in information
include lack of detailed information on latest treatments, QoL, palliation,
communication with health care providers, and advanced directives and
end-of-life care.
Conclusions: While QoL issues for MBC patients/caregivers are well
understood, the resources and commitment to address these issues
effectively are still lacking. Targeted information and support services
addressing QoL needs are as necessary to patients as medical treatments.
BP38
METASTATIC BREAST CANCER IN CANADA: WAITING FOR TREATMENT
Niya Chari
Canadian Breast Cancer Network, Government Relations, Ottawa, Canada
Of the 24,400 women in Canada diagnosed with breast cancer each year,
approximately 5% will have an initial diagnosis of metastatic breast
cancer and 30% of women diagnosed initially with earlier stages of
breast cancer will go on to develop metastatic breast cancer. Although
Abstracts / The Breast 24 S3 (2015) S21–S75
the five year relative survival rate of women diagnosed with metastatic
breast cancer remains only 20%, innovative new therapies have led
to significant advancements in the overall treatment and disease
progression of women living with metastatic disease. Yet despite the
global progress in the development of new treatments for metastatic
breast cancer, access to these new drugs in Canada remains inequitable.
New drugs are approved for sale in Canada through a multi-step process.
First the drugs are assessed by a federal review body, Health Canada,
a process that usually takes between one to two years from the date
of submission by the drug manufacturer. Following this approval, new
drugs must be reviewed by two pan-Canadian assessment bodies to
qualify for listing on the provincial and territorial drug formularies,
which allow patients to access drugs at no cost or at a significantly
reduced cost. Unfortunately, not all provinces and territories choose
to include new drugs on their formularies. If a drug is not listed on a
provincial/territorial formulary, the patient must cover the drug cost
out of pocket or through private insurance, which creates a situation
of unequal access and affordability across Canada. Given the extensive
review process for new treatments, and the vastly differential coverage
for metastatic treatments in provinces/territories across the country,
the Canadian Breast Cancer Network is producing a new report on wait
times for new metastatic breast cancer treatments in Canada. The report
provides a detailed overview of the present situation in Canada for
drug approval and decision-making by provinces and territories about
placing new metastatic drugs on their formularies, as well as an analysis
of the positions of key stakeholders involved in making new drugs
available and affordable. The report also shares a detailed portrait of the
experiences and realities of people living with metastatic breast cancer
and their family caregivers concerning access to new drugs. Utilizing the
data from our report, this session will present an important opportunity
for participants to gain valuable insights into the treatment challenges
facing metastatic breast cancer patients and their families in Canada.
The session will also describe and discuss the potential opportunities for,
challenges around and successful strategies for advocacy to champion
the patient voice and address the urgent treatment needs and concerns
of metastatic breast cancer patients.
PO39
EFFECTIVE ADVOCACY FOR WOMEN WITH METASTATIC BREAST
CANCER: A EUROPEAN PERSPECTIVE
Susan Knox
Europa donna - The European Breast Cancer Coalition, Milan, Italy
EUROPA DONNA - The European Breast Cancer Coalition, (ED) is an
independent, non-profit organisation whose members are affiliated
groups from countries throughout Europe. The Coalition works to raise
awareness of breast cancer and to mobilise the support of European
women in pressing for improved breast cancer education, appropriate
screening, optimal treatment and care and increased funding for
research. EUROPA DONNA represents the interests of European women
regarding breast cancer to local and national authorities as well as to
institutions of the European Union. Through our information, education
and policy/public affairs initiatives, ED is working to ensure improved
services for women with MBC. Our strength lies in having members in
47 European countries working together on the same objectives as the
European coalition, thus enabling us to improve health services and
have a major impact on parliamentarians and health ministries. ED
started by conducting research on MBC in our member countries and
conducting networking groups with members on MBC at our annual
conferences. ED has been working to get the “EU guidelines for quality
assurance in breast cancer screening and diagnosis” implemented since
their publication in 2006 and wrote a short guide to these which we
have translated into 17 languages. These guidelines already contain a
description of key services that should be provided to women with MBC;
however, thus far these have not been implemented in most specialist
breast units. We therefore began communicating this important
S35
information to all our advocates by publishing an annex on MBC so that
our members could advocate for these services nationally. At the same
time, we began a process of educating and convincing parliamentarians
at the European level. A meeting at the European Parliament was held
in February 2014 to raise awareness of the huge gaps in service. Later in
2014, we presented our position again at a European Parliament meeting
and we worked with key MEPs to develop a new Written Declaration on
the fight against breast cancer in the EU, highlighting MBC. This was
launched in April 2015. ED provided the background to MEPs on this
initiative, conducted a week-long exhibition and information session on
it at the European Parliament; our member countries then wrote to their
MEPs to insist on the passage of the declaration giving them 10 reasons
to sign. Passage of the declaration is expected by the end of July. What
is the key to effective advocacy: evidence based information, on-going
education of advocates and the lay public concerning the issues, and
never letting up until the objectives are achieved.
PO40
UNMET NEEDS OF AUSTRALIAN WOMEN WITH METASTATIC
BREAST CANCER WITH FINANCIALLY DEPENDENT CHILDREN: THE
CONSUMER PERSPECTIVE
Danielle Spence1, Michelle Marven1, Karla Gough3, Sanchia Aranda2
1
Breast Cancer Network Australia, Camberwell VIC, Australia; 2Cancer
Institute NSW, Cancer Services & Information, Woolloomooloo, Australia;
3
Peter MacCallum Cancer Centre, Cancer Experiences Research, East
Melbourne, Australia
Background: Breast Cancer Network Australia (BCNA) is the peak
national consumer organisation for Australians affected by breast cancer.
We work to ensure they receive the very best support, information,
treatment and care appropriate to their individual needs. There are no
reliable figures on incidence or prevalence of metastatic breast cancer
in Australia. It is estimated that approximately 15,600 Australians will
be diagnosed with breast cancer this year, of which 10-15% are likely to
develop metastatic disease.
Methods: BCNA distributed an online survey to 1802 BCNA members
identified in our database as having metastatic breast cancer; 582
(32%) participated in the survey. A modified version of the Supportive
Care Needs Survey short-form was administered as part of this survey.
When an unmet need was identified, respondents could nominate their
preferred strategies for addressing unmet needs. Chi-squared tests were
used to assess the association between unmet needs and having (or not
having) financially dependent children.
Results: In total, 474 respondents answered the modified needs
survey. Respondents were from all states and territories in Australia,
with 59% living in a metropolitan area. Most (60%) were aged between
50-69 years, although 24% were under 50 years. The majority (77%)
had been diagnosed with metastatic breast cancer in the preceding
five years, with 8% living for ten years or more. Thirty-three per cent
(n=158) reported having financially dependent children. Women with
financially dependent children reported significantly more unmet needs
in all domains assessed, but the largest differences were observed in
the sexual (‘changes in your sexual relationships,’ 39% versus 16%;
‘changes in your sexual feelings,’ 44% versus 22%; and ‘being given
information about your sexual relationships,’ 32% versus 16%) and
psychological (‘learning to feel in control of your situation,’ 46% versus
29%; and ‘concerns about the worries of those closest to you,’ 63% versus
46%) domains (all p ≤ 0.001). Strategies for self-care were consistently
reported by women as a preferred source of help, along with help from
a relationship counsellor or psychologist.
Conclusions: Women with metastatic breast cancer and financially
dependent children require targeted support and information,
particularly related to, but not limited to, sexual well-being. Based on
these findings BCNA is developing a targeted information and support
strategy, including trialing a free telephone counselling service, to assist
women experiencing these issues.
S36
Abstracts / The Breast 24 S3 (2015) S21–S75
PO41
MIDDLE EASTERN ABC/MBC PATIENTS:OVERCOMING THE
TRIPLE-BURDEN OF STIGMATIZATION, LACK OF INFORMATION AND
RECURRENT ILLNESS
Rania Azmi
“Survive & Thrive” Initiative, For Cancer Patients Support, Middle East,
Kuwait
It is a well-known fact that advanced or metastatic breast cancer (ABC/
MBC) is a complex and significantly serious illness. ABC/MBC patients
usually take the lion share in everything related to their illness, from
treatment challenges to the psychological and emotional burdens. ABC
patients usually feel isolated, under represented compared to breast
cancer patients among the other feelings. In the Middle East; ABC/MBC
patients are even challenged with more factors. In addition to the main
two typical burdens of illness itself and the knowledge that this illness
is incurable; Middle Eastern ABC/MBC patients face the extra burdens of
stigmatization, that sometimes reaches the level of a taboo, and lack of
information if not ignorance about some of the key scientific facts about
their cancer and its treatment options. Over and above, considering that
a large percentage of ABC/MBC patients in the Middle East is from older
generations, this usually means limited access to updated information
that are mostly available in English or other foreign languages than
Arabic. This creates a vicious cycle of miscommunication and misleading
information when patients seek in their own unverifiable information
from the Internet, especially those in their native language. Finally, the
Arabic culture always makes women very protective of their families,
especially their children, where they are always so keen to hide the
cancer recurrence news from their families and as a result they could
face the challenges of feeling isolated or depressed, with no channels
to communicate their needs or feelings. While every effort is made to
address the typical challenges breast cancer patients face in the Middle
East, including education and awareness campaigns, the triple-burden
of stigmatization, lack of information and cancer complications in MBC
patients is mostly overlooked if not considered already an inevitable
causality in the fight against cancer. Accordingly, the patients’ advocacy
efforts in the Middle East should rely on at least three dimensions if the
are to target effectively ABC or MBC patients: 1st: The communication
dimension with the public and between patients-oncologists to
overcome any stigmatization proactively. 2nd: The information bank
dimension where advocacy efforts could mobilize easy-to-understand,
timely and reliable information for the use of MBC patients to help
them and their caregivers in making informed decisions. 3rd: The
cancer treatment dimension, where international efforts are required
to make new treatments accessible to Middle Eastern patients as they
become available with a primary focus on measuring and increasing the
perceived patient’s quality of life.
of patients/caregivers, as well as to explore the patient’s treatment
journey.
Materials and Methods: The MYDC survey, conducted in the United
States between June and August 2014, included women with ABC aged
≥ 21 years, caregivers (aged 18 years) of women with ABC, and medical
oncologists. The survey was administered online, by phone, and by
paper. Patient and caregiver data were not weighted. No estimates of
error can be computed.
Results: Survey respondents included 359 patients, 234 caregivers, and
252 oncologists. Majority of patients felt that it was important to discuss
long-term treatment goals (92%) and alternative/complementary
treatment options (72%) with their doctor at their initial ABC
diagnosis, however, actual discussion happened less frequently (53%
and 26%, respectively). Similarly, while most patients (92%) felt that
conversations regarding the management of treatment side effects (SEs)
were important, only 58% indicated that these conversations actually
took place at their initial diagnosis. Majority of the patients (56%)
and caregivers (74%) did not initially realize the severity of treatment
SEs, with 46% of patients and 67% of caregivers indicating a desire for
more help from their healthcare team in managing SEs. Yet, over 4
of 10 patients (43%) had not always openly discussed SEs with their
oncologist. Nearly all patients (96%) reported experiencing some change
in their appearance and 44% stated that cancer had stolen their dignity.
Although the majority of caregivers (94%) stated that they try to maintain
a positive outlook, 77% reported feeling emotionally burdened and
86% stated that their own life had been negatively impacted. Although
nearly all oncologists (97%) reported that following the journey of their
patients with ABC gave them a greater appreciation of life, 42% felt that
treating these patients had a lot of negative emotional impact.
Conclusions: The MYDC survey provides evidence of communication
challenges and emotional burden faced by patients with ABC and those
caring for patient with ABC (informally as a caregiver or formally as an
oncologist). Improving patient-doctor communication by encouraging
patients and caregivers to ask direct questions regarding treatment goals,
SE management, and emotional burden and by educating oncologists on
gaps in communication with patients regarding these topics could help
in addressing some of the unmet needs of patients with ABC.
PO43
“FIGHT, LIVE, KEEP SMILING”: THE FIRST ITALIAN BLOG ABOUT
METASTATIC BREAST CANCER (MBC) ADDRESSED TO THE GENERAL
PUBLIC. A QUALI-QUANTITATIVE ANALYSIS OF ALL THE COMMENTS
POSTED ONLINE ON THE BLOG OF THE EUROPA DONNA ITALIA MBC
WORKING GROUP
Francesca Balena1, Tiziana Moriconi2, Ilaria Vacca1, Mimma Panaccione1,
Barbara Bragato1, Ivana Policiti1, Sabrina Franci1, Tiziana Farci1
1
Europa Donna Italia, MBC Working Group, Milano, Italy; 2Galileo servizi
editoriali; Salute Seno – D la Repubblica, Milano, Italy
PO42
MAKE YOUR DIALOGUE COUNT SURVEY: ADDRESSING
COMMUNICATION GAPS BETWEEN PATIENTS WITH ADVANCED
BREAST CANCER, THEIR CAREGIVERS AND ONCOLOGISTS AND
UNDERSTANDING INFORMATION AND EMOTIONAL NEEDS TO
IMPROVE TREATMENT AND SIDE EFFECT MANAGEMENT
Helen L. Coons4, Ivis Sampayo3, Victoria Harmer1, Robyn Bell Dickson2
1
Imperial College Healthcare NHS Trust, Charing Cross Hospital, Breast
Care Unit, London, W6 8RF, United Kingdom; 2Nielsen, Youth & Education
Research, New York, NY 10004, USA; 3SHARE, Programs, New York, NY
10036, USA; 4Women’s Mental Health Associates, Health Psychology,
Denver, CO 80204, USA
Background: The needs of patients with advanced breast cancer (ABC)
are distinct from those of patients with early breast cancer and often
remain unaddressed. The Make Your Dialogue Count (MYDC) survey was
conducted to identify communication gaps between patients/caregivers
and oncologists, to understand the information and emotional needs
Metastatic breast cancer patients are often young women, and many of
them have a job, a family and children. Despite this, little is said about
their stories and needs in the media: the advanced cancer is still a taboo
in Italy. In order to overcome this situation, five women of the Europa
Donna Italia MBC Working Group have created a blog on the “D la
Repubblica” website, one of the most popular women’s magazine in the
country. Their goal is to tell their stories of life with MBC, and to get in
touch with many of the 30,000 MBC patients which live in Italy today. At
the moment, this blog is one of the largest online self-help community
dedicated to the needs of advanced/metastatic breast cancer patients
in Italy. Since the blog has been created, in January 2014, it has collected
more than 600 comments, and got 8,793 page views per month and 5,742
unique visitors per month (source: Webtrekk, March 2015). In order to
draw attention to the problems the MBC Italian patients face everyday, and
also to understand how the blog can be supportive, we conducted a qualiquantitative analysis of all the comments. Some of the topics covered are:
“the choice of where to get treatments”; “the relationship with physicians
and with healthcare facilities”, “the relationship with their community”,
“the life with therapies and with the follow-up”, “the sex life”, “the
Abstracts / The Breast 24 S3 (2015) S21–S75
side effects of drugs”, “the daily life”. One of the goals is to draw up the
guidelines for the Europa Donna Italia advocacy activities in the MBC field.
The project was supported by unconditional grant from Amgen.
PO44
IN OUR SHOES: RAISING THE VOICES OF MBC PATIENTS
Lori Marx-Rubiner
METAvivor Research and Support, Annapolis, MD, USA
Objective: The “In Our Shoes” survey was developed as an opportunity
for women and men living with metastatic breast cancer (MBC) to share
their thoughts and concerns related to living with MBC. Areas addressed
include demographic information, the impact of MBC on relationships
with friends and family, the nature of their relationships with healthcare
practitioners, and their understanding of investment in the advocacy
landscape surrounding MBC.
Methods: The survey was distributed in April 2015 via social media,
including posts to the METAvivor and personal blogs, numerous Twitter
and Facebook announcements over the course of 2-3 weeks, promotion
within large pools of advocates including the weekly #BCSM twitter
chat, and word of mouth. Networking with international organizations
was attempted as well.
Results: The survey accrued 370 responses, of which 343 are included in
the data evaluation. (27 respondents indicated that they had not received
a diagnosis of MBC and were therefore excluded from analysis.) The
survey allowed for the inclusion of incomplete responses to encourage
broad participation, and allowed for annotative comments for many
questions in order to capture the experience of MBC patients as they
articulate it. Greater collaboration with international advocacy groups
would provide an understanding of global realities, as well as a basis for
comparing the extent to which MBC patients share similar experiences
based on country and/or region. Respondents were generous in sharing
candid insights about how they cope and adapt to life as a terminal
patients in the context of many of the relationships that surround them,
including family and friends, healthcare providers, and advocates who
work in and on behalf of the MBC community.
PO45
INFORMATION NEEDS OF YOUNG WOMEN WITH METASTATIC
BREAST CANCER TO MANAGE THEIR TREATMENT, SIDE EFFECTS AND
CLINICAL TRIALS
Medha Sutliff, Desiree Walker, Michelle Esser, Jean Rowe, Megan McCann
Young Survival Coalition, National Programs, New York, USA
Background and Methods: Young women (YW) diagnosed with
metastatic breast cancer (MBC) face a set of unique issues and concerns.
Young Survival Coalition (YSC) is the premier global organization
dedicated to critical issues particular to YW and breast cancer. In 2012,
YSC engaged in a two year long process called the Research Think
Tank (RTT) to determine the most pressing research questions in need
of answers. The RTT found that research into MBC in YW was rare and
determined the topic to be a top research priority. After identifying this
priority, from September, 2013 to February, 2014 YSC conducted an online
survey of women diagnosed with any stage of breast cancer before age
of 41, who either had MBC at initial diagnosis or developed it thereafter.
Results: The survey revealed that an overwhelming majority of YW with
MBC searched for information on treatment and prognosis (95%), clinical
trials (69%) and management of side effects (88%). For each category,
between 22 to 33% said there was information they searched for but
could not find. Information found lacking included prognosis statistics,
treatment and side effect information, updates on new treatment and
medical advances, information on different types and locations of
metastases, clinical trial information, information on rare side effects,
and alternative therapies to manage side effects. Seventy-six percent
of respondents looked for information on how long YW are living
S37
with MBC, and 80% said this information would be helpful. There were
frequent comments about outdated information, there being “no hope”
and “scary statistics.” Respondents complained that there is not enough
data that is accurate, easy to understand and scientifically supported.
Information found is too generic and general rather than being specific
to the YW’s situation. YW with MBC had to judge the accuracy of the
information found, especially from news reports. A centralized location
to find information relevant to MBC with easier terminology, a bank
of current research and more information overall that is easy to find
and access would help, according to survey respondents. A greater
focus on YW is also needed. For clinical trials, respondents identified
better search engines, easier to read and understandable materials,
someone to speak with on the phone to help them navigate through trial
information and filter out inapplicable trials, more current information,
one clear resource instead of multiple sources, and listings for MBCspecific clinical trials as helpful tools.
Conclusion: YW living with MBC have important information needs
that are currently unmet. YSC will be updating its on-line information
and website to better meet these needs.
PO46
I AM ANNA: EXPLORING METASTATIC BREAST CANCER THROUGH
THE EYES OF A YOUNG WOMAN
Shawna Ginsberg
Rethink Breast Cancer, Breast Cancer Department, Toronto, Canada
Through research and front-line support work, Rethink Breast Cancer
listens to young women living with metastatic breast cancer voice
their sense of isolation within the breast cancer community. They feel
there is a lack of support and resources available to them that address
their unique needs. In addition to the needs that arise from their age
and life stage, young women living with metastatic breast cancer face
ongoing treatments and their side effects, as well as coping with chronic
disease and end of life issues. Documentary film is a powerful medium
to connect audiences with the experience of the subjects in the film,
which helps raise the awareness and understanding of the issues and
challenges presented. I AM ANNA tells the insightful story of Anna Craig:
a mother, wife, artist, architect and young woman living with metastatic
breast cancer. The film follows Anna’s inspiring journey to create her
legacy by building an addition to her house that fulfills her artistic
dreams and leaves something for her family. Through this process
we watch her help to build a support network for young metastatic
women. The presentation will include a screening of I AM ANNA (30
minutes) followed by a Q&A with Anna Craig, patient advocate and
blogger. Anna will discuss living with metastatic breast cancer as a
young woman, creating a legacy and how film can be used as a resource
in the psychosocial oncology community to open dialogue, explore
challenging issues, provide support and inspire other young metastatic
women to use their voices for change.
PO47
IDENTIFYING DEFICITS AND NEEDS FROM STAKEHOLDERS ABOUT
PALLIATIVE CARE ISSUES
Shankpal Pramod
Health Alert Organisation of India, Health Department, Garud colony,
Deopur, Dhule, India
Objectives: Our Cancer NGO aims to analyzing palliative care issues/
needs and their status. ESMO/WHO urgently needs to focus on
development of palliative care for breast-cancer patients. For developing
nations this approach will certainly have positive impact on breast
cancer management. NGOs working in remote areas can develop policy
paper for implementation in the rural/tribal areas.
Method: Our NGO volunteers and nurses conducted this pilot study
in six rural villages of India. 7 nurses, 2 physicians and 1 counselor
S38
Abstracts / The Breast 24 S3 (2015) S21–S75
participated. 146 patients, 34 caregivers, 18 spiritual/community leaders
participated. Relief of distressing symptoms reported in 80%. Responses
on palliative care analyzed using questionnaires while community/
spiritual leaders participated through focus group discussions. 90%
participants expressed need for model that incorporates palliative
services into the mainstream of medical therapy should be emphasized
as standard care approach.
Results/findings: Poor wellbeing, appetite, pain and fatigue were most
prevalent symptoms reported by the patients. 50% of the patients
reported severe pain and 9% reported no pain. Spiritual pain control
had highest correlation to QOL in comparison to functional, emotional,
physical and social wellbeing. 90% of patients and caregivers reported
free communication about illness. We also need to modify attitudes
of caregivers towards psychosocial needs of breast cancer patients
and their families. Breast cancer care hospitals must have separate
departments for handling these issues.
Conclusions/recommendation: This study gives demographic picture
of terminal cancer patients and family caregivers in public healthcare
system and some aspects of palliative care. Resource-poor-nations
need NGO to develop such programs in absence of governmentrun-healthcare-setup. We NGO activists need conference to discuss
our project ideas/concerns/difficulties with senior researchers from
USA/EUROPE. ESO must take initiative in propagating such efforts in
developing-nations. Development of comprehensive breast cancer
service program is distant dream in resource poor nations. We NGO
patient advocates need international funding support for palliative care
programs.
PO48
TERMINOLOGY USED IN ADVANCED BREAST CANCER AND THE NEED
FOR CONSISTENCY
Maria Leadbeater1, Tara Beaumont2
1
Ashgate Hospice, Macmillan Clinical Nurse Specialist Palliative Care, Old
Brampton, Chesterfield, UK; 2South West Yorkshire Partnership NHS Trust,
Macmillan Palliative Care, Barnsley, South Yorkshire, UK
Terminology used in oncology is frequently derived from ancient Greek,
E.g. the term ‘metastatic’ meaning to ‘change place’. The past decade
has seen many advances in both identification of sub types of breast
cancer and its treatments. Consequently terminology to describe breast
cancer has evolved; both patients and health professionals use a range
of terms to describe the disease, in addition to the traditional TNM
classification of malignant tumours. There is a need for terminology to
clearly explain the stage of breast cancer and individual assessment, to
appreciate the complex prognostic factors involved and an awareness of
potential difficulties, which can arise when terms are misinterpreted. A
survey of breast care nurses found wide variations in terminology used
and the need for consistency and clarity when talking with patients and
professionals. The term ‘metastatic’ was widely used by international
organisations attending a global advocacy working group in New York
(MBCAWG 2009). In the UK the National Institute for Health and Clinical
Excellence (NICE 2009) published guidance on advanced breast cancer
and the European School of Oncology Advanced Breast Cancer(ABC)
guidelines (2012)clarifies the term ABC includes locally advanced,
inoperable breast cancer. In the UK, cancer charities frequently
use the term ‘secondary’ which can be ambiguous, with patients
reporting confusion about what is relevant for them when accessing
information. A survey of 46 breast care nurses was undertaken, the
findings demonstrated 77% used more than one term when talking to
colleagues, terms ranged from metastatic 41%, secondary 35%, advanced
breast cancer 19% and stage 4 5%. Other terms used when talking with
colleagues included recurrence 1%, distant spread 1% and aggressive
1%. When talking with patients 54% of nurses used the term secondary
with advanced breast cancer used by 14% and other terms used were
recurrence or distant spread. 15% of nurses reported the term secondary
had other meanings which included; a second primary cancer or
secondary care. Advanced breast cancer describes a complex, disease
and individual assessment of the patients understanding of their illness
is essential. Arguably defining the precise terminology may not be as
important in the treatment setting where each person’s treatment is
individually planned, based on their specific diagnosis. However, there
can be difficulty in translating clinical trial findings to the patient
populations and from the perspective of patient information it is
important correct terminology is used to ensure the patient is receiving
appropriate information, which is one of the recommendations for
clinical practice.
PR49
GETTING BACK INTO LIFE
Shirley Bianca Mueseler
Zebra Breast Cancer Counselling Centre, Dusseldorf, Germany
I am a two-time breast cancer survivor, Dutch, living in Cologne,
Germany. In 2000 I was diagnosed with a collision tumor, triple-negative
and a third tumor, which was benign. All three cosily nested in one
breast. Exactly 5 years later I had a second cancer. After my first surgery
with immediate partial reconstruction, I went through chemotherapy
and radiation. THIS TRACK WAS A MARATHON AND NOT A SPRINT.
Breast cancer changed my life completely. One of my new challenges
was painting; I had never painted before. Images were created in my
subconscious. I decided to make a story out of it, just for myself. 22
Paintings with the title “Message of Hope”… my healing journey. Then
my friends told me: “you have to do something with it”. So I began to
contact international cancer organisations, they were interested and
invited me to present my Slideshow. Since 2010 ECCO//ESMO//ASCO//
ECPC// EUROPA DONNA//REACH TO RECOVERY INTERNATIONAL// VITAL
OPTIONS INTERNATIONAL+++ have been supporting and inviting me to
speak about “Getting back into Life”, as well as to present and exhibit my
survivorship story “Message of Hope”. My mission is to encourage breast
cancer patients and motivate them to unlock their creative potential,
which could heal both soul and body. My project is to reinforce the
connection between Art, Cancer and Patients Supportive Care. My goal
is to make a difference in the Breast Cancer Community through creative
expression. I believe ART IS LIFE and LIFE IS ART. Just recently I decided
to commit myself in a unique project “Global License in Oncoplastic
Surgery”. Initiated by 2 Doctors. They will present this issue for the first
time in a special session at the Barcelona Breast Meeting BBM in March.
My painted poster “The Expert Eye” will be incorporated: Using my
Artwork to Speak Out. There is no official Oncoplastic Surgery Specialty
Training. This need to be created as an integral part of Breast Surgical
Training worldwide and be a concept of WHO to be established. We
patients need the availability of a reliable Global Register of Specialists.
Oncoplastic Surgery can be involved in any stage of Breast Cancer. OPS
was originally conceived to help patients with large tumors, locally
ADVANCED BREAST CANCER.WHAT IS MY PASSION? To inspire breast
cancer patients how to express their feelings thru Art. To advise breast
cancer patients finding Specialists in Oncoplastic Breast surgery so that
they can be confident to receive top health care. There are Too Many
Mastectomies, Too Many Mutilations and Too Many Breast Centres
WITHOUT Licensed Specialists in Oncoplastic Breast Surgery. THIS
breaks my heart!
PR50
PSYCHOLOGICAL SUPPORT TO CANCER PATIENT THROUGH
VOLUNTEERS AND SURVIVORS
Aditya Manna
MAS Clinic and Hospital, Oncology Dpt., Purba Medinipur, India
Introduction: The diagnosis of cancer is like a bolt from the blue to the
patients and relatives. It causes tremendous mental stress and panic.
Taking the patient and the family members out of such mental and
familial stress is a very difficult job.
Abstracts / The Breast 24 S3 (2015) S21–S75
Aim: The idea is to overcome such mental and familial stress utilizing
the services of volunteers and survivors as doctors are too busy to be
able to spend quality time with the patients.
Method: We have a substantial flow of cancer patient as oncology unit of
MAS Clinic, India. The idea is to train volunteers to do this communicating
under the guidance of doctors. Through regular orientation get together
of new patient and their relatives with survivors and volunteers.
Result: Till the end of 2014 we have been able to successfully do this
kind of job in a substantial number of patients where come to our notice.
Conclusion: Psychological support is an essential element of holistic
patient care in diagnosis of cancer. And this can be effectively done
through the help of volunteers and survivors also.
Clinical Issues: Medical Oncology
S39
Conclusions: Symptoms increase during the first 3 mts of 1st-line
treatment and differ between pts receiving monoCT or ET for ABC.
In contrast, no change in mean global QoL can be detected. Our data
indicate that global QoL alone might not be sufficient to compare
treatments and should not serve as the sole base for decision making.
BP52
IS THERE A DIFFERENT TREATMENT RESPONSE BETWEEN VISCERAL
AND NON-VISCERAL METASTATIC BREAST CANCER: A SYSTEMATIC
LITERATURE REVIEW OF REGISTRATION TRIALS
Rachel Würstlein, Maximilian Bardenhewer, Alexander König,
Thomas Kolben, Caroline Gehring, Nadia Harbeck
Medical Center of the Ludwig-Maximilians-University, Department for
Gynecology of Obstetrics and Comprehensive Cancer Center of LMU,
Munich, Germany
OR51
NO IMPACT OF INCREASING SYMPTOMS ON QUALITY OF LIFE?
LONGITUDINAL DATA FROM THE GERMAN MALIFE-PROJECT ON
PATIENTS RECEIVING MONOCHEMO- AND ENDOCRINE TREATMENT
FOR ADVANCED BREAST CANCER – RESULTS FROM THE TMK
REGISTRY GROUP
Norbert Marschner4, Arnd Nusch3, Thomas Decker2, Michaela Münz1,
Lisa Kruggel1, Martina Jänicke1
1
iOMEDICO, Clinical Epidemiology and Health Economics, Freiburg i. Br.,
Germany; 2Onkologie Ravensburg, Onkologie, Ravensburg, Germany;
3
Praxis für Hämatologie und internistische Onkologie, Hämatologie und
internistische Onkologie, Velbert, Germany; 4Praxis für interdisziplinäre
Onkologie & Hämatologie, Interdisziplinäre Onkologie & Hämatologie,
Freiburg i. Br., Germany
Introduction: Systemic treatment of advanced breast cancer (ABC)
aims to prolong survival while maintaining or improving quality of
life (QoL). Clinical trials often report no difference in QoL between
treatments, even in case of differing side effect profiles. Can patientreported outcomes (PROs) in routine practice be used to better evaluate
the impact of different treatments on QoL?
Patients and Methods: MALIFE is conducted with the Tumour Registry
Breast Cancer II (TMK II), an ongoing, prospective, national, observational
study of patients (pts) with breast cancer recruited at the start of (neo)
adjuvant or palliative systemic therapy in Germany. Besides pts’ and
tumor characteristics, all systemic therapies and outcome data are
recorded. Pts regularly receive a set of validated questionnaires and some
specifically constructed PRO measures. By 2016, 2000 pts will have been
recruited by more than 250 office-based medical oncologists. In this
interim analysis, data on global QoL (FACT-G) and symptoms (EORTC
QLQ-BR23 - BRST-Score, FACT-Taxane and Brief Fatigue Inventory (BFI))
are compared during the first 6 months (mts) of ABC treatment with
monochemo- (monoCT, n=166) or endocrine therapy (ET, n=95). A 10%
change is considered clinically relevant.
Results: Pts were ø 67/60 years old (monoCT/ET) at the start of 1st-line
therapy. Questionnaire return rate was 80/82% and 64/68% after 3 and
6 mts (monoCT/ET). At the 6 mts survey, 64% of patients continued 1stline therapy, 24% had changed treatment strategy. Change in treatment
and return rate did not affect the overall data presented. About 50% of
pts receiving monoCT reported clinically relevant increased symptoms
(BRST-Score), especially dysgeusia, irritated eyes and hair loss, as well
as polyneuropathy (FACT-Taxane, subscale polyneuropathy) after 3 mts
of treatment. While polyneuropathic symptoms remained at 6 mts,
other assessed symptoms decreased. Mean impairment of daily life by
fatigue (mean BFI interference score) increased in the first 3 mts, but
had decreased at 6 mts. About 30% of pts receiving ET reported clinically
relevant increased symptoms at 3 mts, mainly hot flushes, irritated eyes
and hair loss. At 6 mts, 30% of pts again reported increasing hot flushes.
Mean impairment of daily life by fatigue increased at 3 and 6 mts. Mean
global QoL (FACT-G) remained unchanged during the first 6 mts of
monoCT or ET, and did not differ between the two treatment strategies.
Introduction: Differential efficacy of newly registered therapies
in subgroups of metastatic breast cancer (mBC) is an important
consideration for their subsequent use in clinical practice. Such
subgroup analyses are often exploratory, rarely statistically adequately
powered and may thus be misleading. In a systematic literature review,
we evaluated differences in outcome regarding progression free survival
(PFS), time to progression (TTP), overall survival (OS) and visceral versus
non-visceral disease. The impact of HER2- and hormone receptor-status
was also considered.
Methods: A systematic literature search (6362 hits) in the meta-Database
PubMed was performed for the last 20 years. 257 studies (n=126,291)
were included for further analysis. 69 studies had published data for
visceral (i.e. presence of visceral metastases independent of the presence
of other metastasis sites) vs. non visceral (i.e. non-visceral metastases
in the absence of visceral involvement) disease including phase III trials
plus studies that had further used their data. Out of these 69 studies we
selected n=16 studies (n=13,083) by considering (A) the medical product’s
professional information and (B) the decision of the U.S. Food and Drug
Administration or the European Medicine Agency for the approval of
the therapeutic agents which are now used in treatment of mBC. All
selected 16 studies had looked at the endpoints mentioned above. In
order to achieve comparability, we extracted the information of hazard
ratios (HR), confidence intervals (CI) and times in weeks (if available) for
PFS, TTP, OS of the entire study population, which was divided into three
groups: HER2-positive, HER2-negative, unknown HER2 status.
Results: No statistically significant difference in treatment response
was found in mBC patients looking at HRs and CIs. Relevant, yet not
statistically significant differences were found in the specific response
of visceral metastases to modern combination therapies, especially in
HER2-positive breast cancer: There was a benefit regarding OS using
lapatinib combined with trastuzumab or trastuzumab and docetaxel
combined with pertuzumab. Additionally, in two chemotherapy trials,
there was a numerical difference between therapy response in visceral
vs. non-visceral metastases regarding PFS in the unknown HER2 group,
and regarding OS in the HER2 negative group.
Conclusions: In the subgroup analyses, we did not find any significant
differences in response rates for visceral vs. non-visceral metastasis. For
targeted therapies based on a biomarker, there seems to be a beneficial
effect of combination therapies regarding OS in visceral disease. At the
present time, metastasis localization should not be used as a predictive
marker for choice of systemic therapy in mBC.
S40
Abstracts / The Breast 24 S3 (2015) S21–S75
PO53
CLINICAL IMPACT OF METRONOMIC ORAL COMBINATION
CHEMOTHERAPY WITH CAPECITABINE AND CYCLOPHOSPHAMIDE IN
PATIENTS WITH METASTATIC BREAST CANCER
Miwa Fujihara, Shoichiro Ohtani, Mistuya Ito, Yukiko Kajiwara,
Yuri Yoshimura
Hiroshima City Hiroshima Citizens Hospital, Breast Surgery, Moto-machi,
Naka-ku, Hiroshima, Japan
Background: Interest in oral agents for the treatment of metastatic breast
cancer (MBC) has increased due to patients’ preference for oral therapy
over intravenous (IV) therapy. However, although the quality of life is
better with oral therapy, patients are generally unwilling to sacrifice
efficacy when prioritizing oral over IV therapy. Capecitabine (X) and
cyclophosphamide (C) can be orally administered and have synergistic
effects with non-overlapping toxicities in patients with MBC. Clinically,
we have observed heavily pretreated patients with MBC with excellent
efficacy with XC therapy and less toxicity. In this study, we retrospectively
evaluated the efficacy and safety of an oral combination of XC therapy.
Methods: A retrospective review was conducted of human epidermal
growth factor receptor (HER)2-negative patients with MBC who received
XC therapy at Hiroshima City Hiroshima Citizens Hospital; adverse
events, time to progression (TTP), and overall survival (OS) were used
to evaluate the clinical response to XC therapy. Doses of X and C were
determined according to the phase I results from the Kyushu Breast
Cancer Study Group (Ohno S et al. Anticancer Research, 2007). A dose
of 1657 mg/m2/day capecitabine and 65 mg/m2/day cyclophosphamide
was given orally twice daily for 14 days. The treatment was repeated
at 3-week intervals until disease progression or treatment interruption
due to adverse events.
Results: Between 2009 and 2015, we analyzed 71 patients with
MBC (median age, 56; range, 27–85 years), with a median previous
chemotherapy regimen (range, 0–7). The overall response rate was
40.3%; the response rate (RR) was 41.2% in hormone receptor (HR)positive cancers and 35.0% in HR-negative cancers. The median TTP was
273 days [95% confidence interval (CI), 224–363 days) and median OS
was 1045 days (95% CI, 665–1749 days). The median TTP was 197 days
in patients who required extended interval or dose reduction and 326
days in patients on standard treatment regimes (p = 0.0047). Further,
median TTP was 197 days in patients who suffered from hand-foot
syndrome (HFS), whereas 284 days in patients without HFS (p = 0.0362).
Grade 3 or 4 leukopenia was observed in 12 cases (16.9%), neutropenia
in 10 (14.1%), anemia in 3 (4.2%), and thrombocytopenia in 0 cases (0%).
Non-hematological toxicities were mild. HFS was observed in 14 cases
(19.7%), although no cases of grade 4 HFS occurred. Only two patients
with grade 3 hemorrhagic cystitis interrupted therapy due to adverse
events (cyclophosphamide side-effects).
Conclusion: Oral XC therapy was very effective with less toxicity in
HER2-negative MBC. XC therapy may be a promising oral chemotherapy
regime in light of its cost-effectiveness, quality of life, and preference of
patients with MBC.
PO54
A RETROSPECTIVE MULTICENTER OBSERVATION STUDY IN
METASTATIC BREAST CANCER PATIENTS: COMPARATIVE ANALYSIS
ON EFFICACY OF ERIBULIN MESYLATE WITH TAXANE REGIMENS
(INCLUDING COMBINATION WITH BEVACIZUMAB)
Yasuko Kikuchi3, Kazuo Shirakawa1, Hajime Kanauchi2, Takako Wakeda3,
Takayoshi Niwa3, Kotoe Nishioka3, Keiichirou Tada3, Yoshihiro Uchida1
1
International University of Health and Welfare Mita Hospital, Breast
Center, Tokyo, Japan; 2Showa General Hospital, Breast and Endocrine
Surgery Department, Tokyo, Japan; 3The University of Tokyo Hospital,
Breast and Endocrine Surgery Department, Tokyo, Japan
Aim: Recently approved eribulin (Eri) has been shown to improve overall
survival (OS) in phase 3 study with metastatic breast cancer (MBC)
patients (pts). But head-to-head studies on OS have not been reported
yet, comparing Eri with taxane regimens (TAX) including combination
of bevacituzumab (B+T) which are standard therapeutic regimens for
the early line MBC pts. Here we presented comparative analysis on
efficacy of Eri with TAX in a retrospective multicenter observation study
in the early line MBC pts.
Method: MBC pts who received Eri or TAX; taxane monotherapy (nabpaclitaxel and docetaxel: T) or B+T between August 2011 and March
2014 in our institute were analyzed in this study. Kaplan-Meier method
was utilized to estimate median PFS and OS and log-rank test was used
to compare OS and PFS between regimens. Survival post progression
(SPP) was also analyzed to investigate the effect of post-treatment.
Results: This study identified 192 MBC pts who received Eri (103
pts) or TAX (89 pts). Median age was 60 and 63 years for Eri and TAX,
respectively. Median number of prior chemotherapy was one for each
regimen. Median OS were 876, and 578 days for Eri and TAX, respectively.
Eri significantly prolonged OS compared with TAX (p<0.001). Median
PFS were 245 and 148 days for Eri and TAX, respectively. In subgroup
analysis B+T prolonged PFS but did not prolonged OS, compared with
T as already reported. Eri significantly prolonged OS compared with T
and B+T (Eri vs T; p<0.01, B+T; p<0.001). SPP of Eri was superior to TAX,
T or B+T.
Conclusions: This study showed that Eri improved OS significantly
compared with TAX and B+T. OS prolongation by Eri was supposed to
correlate to SPP prolongation. This study warrants further evaluation of
eribulin in early line MBC patients.
PO55
EFFICACY AND SAFETY OF ERIBULIN IN ANTHRACYCLINE AND
TAXANE-PRETREATED PATIENTS: RUSSIAN EXPERIENCE
Elena Kovalenko, Lydmila Manzyuk, Elena Artamonova
Russian Scientific Oncological Center, Research of New Antitumor Agents,
Moscow, Russian Federation
Background: Eribulin is a novel antimicrotubule drug. We assessed
efficacy and safety of eribulin in anthracycline- and taxane pretreated
patients.
Methods: Twenty patients with a median age of 55 yrs (43-71 yrs) and
ECOG status 0-2 were assessed (10 patients from a randomized 301
study, 10 patients from everyday practice). Eleven (55%) patients were
ER/PR-positive, 8 (40%) – triple-negative, 1 (5%) – HER2-positive. Most
of the patients (70%) had visceral metastases. Eribulin was administered
as 1st line in 3 (15%) patients, as 2nd – in 3 (15%) patients, as 3rd and
later lines – in 14 (70%) patients. A total of 84 cycles were administered
(2-9, median 4).
Results: Efficacy was assessed every 6 weeks. Objective response
occurred in 5 (25%) patients (2 ER+ patients with lymph node and liver
metastases and in 3 triple-negative patients with visceral and skin
metastases). Stable disease registered in 8 (40%) patients, progression–
in 7 (35%). Median duration of response was 16 weeks (6-36 weeks),
median PFS was 12 weeks (6-52 weeks). The most common type of
toxicity was hematologic. Neutropenia grade III-IV was observed in 7
(35%) patients in 10 (12.0%) cycles, but no febrile neutropenia registered.
One (5%) patient experiences fatigue grade II and 1 (5%) – abdominal
pain grade II associated with constipation. Peripheral neuropathy grade
II was observed in one (5%) patient. Dose reduction due to toxicity was
performed in 4 (20%) patients, dose delay – in 1 (5%) case. No further
dose reductions were needed. Overall the drug was well tolerated.
Treatment was never withdrawn due to toxicity.
Conclusions: Eribuline is a treatment of choice after progression on
anthracyclines and taxanes. The drug is safe and effective in this hardto-treat population.
Abstracts / The Breast 24 S3 (2015) S21–S75
PO56
PO57
BOLERO-4: A PHASE 2, OPEN-LABEL, MULTICENTER, SINGLE-ARM
TRIAL INVESTIGATING THE EFFICACY AND SAFETY OF FIRST-LINE
EVEROLIMUS (EVE) IN COMBINATION WITH LETROZOLE (LET) IN
POSTMENOPAUSAL PATIENTS (PTS) WITH ESTROGEN RECEPTOR–
POSITIVE (ER+), HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR
2–NEGATIVE (HER2–) METASTATIC OR LOCALLY ADVANCED
UNRESECTABLE BREAST CANCER (BC)
CLINICAL EFFICACY OF LH-RH ANALOGUE PLUS AROMATASE
INHIBITOR IN PREMENOPAUSAL WOMEN WITH ESTROGEN
RECEPTOR–POSITIVE ADVANCED BREAST CANCER: A
SINGLE-INSTITUTION RETROSPECTIVE STUDY
Thomas Bachelot1, Cristian Villanueva8, Melanie Royce9, Marc Debled4,
Felipe Melo Cruz5, Roberto Hegg3, Thomas Brechenmacher7,
Corinne Manlius6, Francois Ringeisen6, Fatima Cardoso2
1
Centre Léon Bérard, Breast Cancer Unit and Clinical Trial Unit, Lyon,
France; 2Champalimaud Clinical Care, Breast Unit, Lisbon, Portugal;
3
Hospital Perola Byington/FMUSP, Centro de Referência da Saúde da
Mulher, São Paulo, Brazil; 4Institut Bergonié, Medical Oncology, Bordeaux,
France; 5Instituto Brasileiro de Controle do Cancer, Clinical Oncology,
Mooca, Brazil; 6Novartis Pharma AG, Oncology, Basel, Switzerland;
7
Novartis Pharma S.A.S., Oncology, Rueil-Malmaison, France; 8University
Hospital of Besançon, Service d’Oncologie Médicale, Besançon, France;
9
University of New Mexico Cancer Center, Internal Medicine, Albuquerque,
New Mexico, USA
Endocrine therapy (ET) is the standard of care for postmenopausal,
hormone receptor–positive (HR+), HER2– advanced BC (ABC); however,
resistance to ET frequently develops. One possible mechanism of this
resistance is the cross talk between ER signaling and the PI3K/AKT/
mTOR pathway. Efficacy of EVE plus exemestane (EXE) vs placebo
plus EXE was established in the pivotal phase 3 BOLERO-2 trial in
women with HR+ ABC progressing on ET, with a statistically significant
increase in median progression-free survival (PFS) of 4.6 months (local
assessment), and a non-statistically significant improvement in median
overall survival of 4.4 months. Exploratory subset analysis indicated a
significant PFS benefit in women who received EVE plus EXE as first-line
therapy in the ABC setting. The activity of LET in the first-line setting is
well documented, and the safety and efficacy of EVE plus LET has been
demonstrated in the neoadjuvant setting in postmenopausal women
with HR+ BC. BOLERO-4 (NCT01698918) is investigating the efficacy and
safety of first-line EVE plus LET and the potential benefits of continuing
EVE plus ET beyond initial disease progression. Postmenopausal women
with ER+, HER2– metastatic or locally advanced BC with no prior therapy
for advanced disease receive EVE (10 mg/day) plus LET (2.5 mg/day) until
first disease progression. Thereafter, pts have the option to receive EVE
plus EXE (25 mg/day) until further disease progression or unacceptable
toxicity; EVE plus EXE is not offered to pts who discontinue therapy
because of unacceptable toxicity in the first-line setting. The primary
endpoint is PFS in the first-line setting. Secondary endpoints include
overall response rate (ORR), clinical benefit rate (CBR), and safety in
pts receiving EVE plus LET in the first-line setting and PFS, ORR , CBR,
and safety in pts receiving EVE plus EXE in the second-line setting. The
effectiveness of an alcohol-free 0.5-mg/5-mL dexamethasone oral rinse
to reduce the severity and/or duration of stomatitis is being evaluated in
a subpopulation of pts in countries where the oral rinse is commercially
available (United States). The Oral Stomatitis Daily Questionnaire is
being collected for all pts who experience stomatitis. Exploratory
endpoints include biomarker analysis of bone resorption/formation
and evaluation of additional biomarkers for further elucidation of
disease characteristics. The trial opened for enrolment in Europe,
Asia (including Japan), and the Americas in the first quarter of 2013.
Enrolment was completed in December 2014 (N=202). BOLERO-4 will
report in 2016 on the efficacy and safety of first-line EVE plus LET in the
metastatic BC setting as well as the efficacy of continuing EVE-based
therapy following initial disease progression.
S41
Toshiaki Utsumi, Naomi Kobayashi, Masahiro Hikichi, Kaori Ushimado,
Yuki Ri
Fujita Health University, Breast Surgery Department, Aichi, Toyoake, Japan
Background: A combination of an LH-RH analogue and an aromatase
inhibitor (AI) is a promising option for treatment in premenopausal
women with estrogen receptor (ER)–positive metastatic breast cancer.
This study aimed to evaluate the efficacy and safety of an LH-RH
analogue plus an AI in premenopausal women with metastatic breast
cancer in a single institution.
Material and Methods: Between October 2010 and December 2014, 18
premenopausal women with ER–positive metastatic breast cancer were
treated with an LH-RH analogue plus an AI as a second- or third-line
endocrine therapy at Fujita Health University Hospital. Four patients
who had bilateral breast cancer were excluded from analysis. We present
the single-institution, retrospective, experience of an LH-RH analogue
plus an AI in a total of 14 premenopausal women with metastatic breast
cancer. Survival curve was generated using the method of Kaplan-Meier.
Statistical analyses were carried out with PASW Statistics18 software.
Results: Median age was 44 (range; 34-50). Thirteen patients had
ER+/progesterone receptor (PgR)+ disease. One had ER+/PgR- disease.
All patients had HER2 negative disease. Two (14.3%) of the patients
presented with stage IV disease, while the rest experienced recurrence
after earlier treatment of stage II disease. The sites of metastasis were
bone in 8 patients, lung in 5, lymph nodes in 4, pleura in 2 and liver in 1.
Overall, the last endocrine therapy before an LH-RH analogue plus an AI
was an LH-RH analogue plus tamoxifen in 13 patients and tamoxifen in
1. All patients received leuprorelin. Nine patients received anastrozole
and 5 received letrozole. Two patients experienced a partial response
and 6 patients experienced stable disease 6 months or longer, giving
an overall clinical benefit rate of 57.1%. The median progression free
survival time was 12.5 months (range; 2.3-55.8). An LH-RH analogue
plus an AI was well tolerated; no grade 3-4 toxicities were reported and
none resulted in discontinuation of treatment.
Conclusions: Our data suggests that a combination of an LH-RH
analogue and an AI is an effective and well-tolerated treatment in
premenopausal women with ER–positive advanced breast cancer.
PO58
DOES PREVIOUS NEOADJUVANT/ADJUVANT TRASTUZUMAB
INFLUENCE THE DISEASE OUTCOME OF METASTATIC HER2
POSITIVE BREAST CANCER PATIENTS TREATED WITH FIRST LINE
TRASTUZUMAB AND CHEMOTHERAPY
Snezana Milosevic, Nemanja Stanic, Ivana Bozovic-Spasojevic,
Zorica Tomasevic, Snezana Susnjar
Institute for Oncology and Radiology of Serbia, Daily Hospital for
Chemotherapy, Belgrade, Serbia
Introduction: Until recently first line trastuzumab-based therapy had
been the standard of care for women with HER2-positive metastatic
breast cancer (MBC). The aim of this analysis was to investigate if
previous neoadjuvant/adjuvant trastuzumab therapy influenced the
disease outcome in patients (pts) treated with first/line trastuzumab
and chemotherapy (CT) for metastatic breast cancer.
Patients and Methods: We analyzed a group of HER2 positive MBC pts
treated with trastuzumab in combination with anthracycline and/or
taxanes during 2014 at Institute for Oncology and Radiology of Serbia.
All of them had their receptor (ER/PR/HER2) status determined from
primary tumors and for some of them re-biopsies with determination
of ER/PR/HER2 were done. HER2 status was defined as ICH 3+ or IHC2+/
CISH+ or SISH+. We looked at overall response rate and progression -
S42
Abstracts / The Breast 24 S3 (2015) S21–S75
free survival (PFS), defined as a period from the first therapy cycle
administration until disease progression (PD). Statistics included Kaplan
Meier test and Log Rank tests).
Results: We identified 80 HER2 positive MBC pts treated with firstline trastuzumab therapy in combination with anthracyclines and/
or taxanes (paclitaxel or docetaxel) of median age of 53 years (range
26-74). At the time of diagnosis 35/80 (44%) had early-stage BC, 11/80
pts (14% ) locally advanced BC and 34/80 pts (42%) was diagnosed with
metastatic disease. Rebiopsies were done in 17 pts with the confirmation
of HER2 positive BC. Eleven out of 80 pts (14%) were treated with firstline trastuzumab in combination with anthracyclines and taxanes
and in 69/80 pts (86%) trastuzumab was combined with taxanes only.
Median number of docetaxel cycles were 7 (range 4-8) and of weekly
paclitaxel were 9 (range 6-12), and after cessation of CT the treatment
in pts w/o PD was continued with trastuzumab alone, or trastuzumab
with endocrine therapy if HR positive. Among pts diagnosed with stage
1-3 BC 18/46 (39%) received neoadjuvant/adjuvant trastuzumab with
average 14 cycles. All patients with ER and/or PR positive BC received
adjuvant endocrine therapy. Median number of first-line trastuzumab
cycles was 18 (range 2 - 104). Treatment responses were as follows: CR
in 9/80 pts (11%), PR in 23/80 pts (29%), SD ≥6 mos in 43/80 pts (54%),
and PD as best response had 5/80 (6%) pts. Median PFS for all group
of HER2MBC was 18 mos (95%CI 11.13-24.87). There was a significantly
reduced PFS for pts previously treated with neoadjuvant/adjuvant
trastuzumab in comparison with trastuzumab naive pts (14 mos 95%CI
10.9 – 19.3 vs. 29 mos, 95%CI 38.6–60.1); Log-rank, p<0.01.
Conclusion: It seems as if pts with HER2 positive MBC who had been
previously treated with neoadjuvant/adjuvant trastuzumab derived less
benefit from first-line trastuzumab therapy.
PO59
DURABLE REMISSIONS WITH TRASTUZUMAB TREATMENT FOR HER2
POSITIVE METASTATIC BREAST CANCER – SINGLE CENTER EXPERIENCE
Zoran Tomasevic, Zorica Tomasevic, Dobrica Neric, Snezana Milosevic,
Bozovic-Spasojevic Ivana, Zdrale Zdravko, Aleksandra Sarcevic,
Daniela Kolarevic
Institute for Oncology and Radiology of Serbia, Daily Hospital, Belgrade,
Serbia and Montenegro
Background: Trastuzumab improves response and survival in patients
with HER2+ metastatic breast cancer. In this study, we examined patients
who had non-progressive disease for at least 2 years after diagnosis of
inoperable loco-regional recurrent or metastatic breast cancer under
continuous trastuzumab treatment. Primary goal is to assess the longterm outcome of patients with durable response to trastuzumab.
Methods: Between 2005 and May 2015, 23 patients with HER2-positive
inoperable locally recurrent or metastatic breast cancer and nonprogressive disease for at least 2 years under first line trastuzumab
treatment were consecutively documented at the Institute for Oncology
and Radiology of Serbia. Treatment was initiated with paclitaxel/
trastuzumab, and continued with trastuzumab ± hormonal treatment
after median 18 weekly doses of paclitaxel (16-30). Hormonal treatment
is accompanied trastuzumab in 11/23 patients (47.8%).
Results: Median age was 53 years. Metastatic disease was diagnosed at
initial presentation in 7/23, and at relapse in 16/23 patients. Metastases
were present in the liver (6), lungs (5), bones (9), soft tissues (6), CNS
(1), and 12/23 patients have multiple locations of metastases. Remission
was confirmed in 15/23 patients (65.2%), with 10 complete remissions
(43.4%). Median duration of response is 43+ months. The median duration
of trastuzumab is 48 months (range 24-120 months+). Progression is
confirmed in 4/23 (17.4%) patients; 2 with liver metastases, and 2 with
soft tissue metastases. Median duration of trastuzumab treatment in
patients with progression was 26 months (25-28). There were no deaths
due to metastatic breast cancer at the time of this analysis. There was no
cardiac toxicity mandating trastuzumab cessation.
Conclusion: Trastuzumab can induce durable responses in a subset of
patients with HER2 positive metastatic breast cancer. According to the current
recommendations, trastuzumab should be continued until progression.
PO60
THE ROLE OF LAPATINIB IN THE MANAGEMENT OF HER2-POSITIVE
METASTATIC BREAST CANCER: A REVIEW OF A SINGLE INSTITUTION’S
EXPERIENCE DURING THE TRASTUZUMAB AND LAPATINIB ERA
Junichiro Watanabe, Satomo Matsuo
Shizuoka Cancer Centre, Breast Oncology Department, Shizuoka, Japan
Background: Since new monoclonal antibodies, such as pertuzumab
and ado-trastuzumab emtansine, are now being introduced, the practice
treating HER2-positive metastatic breast cancer (HER2+MBC) is now
changing dramatically. We herein review our experiences during the
trastuzumab (TRA) and lapatinib (LAP) era with the aim of evaluating
the clinical significance of LAP use in the treatment of HER2+MBC.
Patients and Methods: We reviewed our medical records for 140
HER2+MBC patients who were treated between September 2002 and
November 2014. The COX regression analyses were applied to identify
the risk factors for survival, and the Kaplan-Meier method with a logrank test was utilized to evaluate the overall survival (OS).
Results: The characteristics of the 140 HER2+MBC patients were as
follows: median age at the diagnosis of MBC, 54 years (range 31-76);
primary advanced disease, 43 cases (30.7%), inflammatory appearance,
9 cases (6.4%) and estrogen receptor (ER) positive, 54 cases (38.6%). The
metastatic site(s) at the diagnosis of MBC were as follows: lung 43 cases
(30.7%); liver 42 cases (30.0%); bone 51 cases (36.4%) and brain 9 cases
(6.4%). All patients received TRA-based therapy, and 52 (37.1%) patients
received LAP-based regimen(s). Within the observation period, 28
luminal-HER2 and 40 HER2+, for a total of 68 (48.6%) patients, developed
brain metastasis (BM), with a median time to BM of 1,612.0 and 1,149.0
days, respectively. The median OS from the diagnosis of HER2+MBC
was 1,526.0 days (95% confidence interval [CI], 464.0-4498.0). The
multivariate COX regression analyses disclosed that the patients who
received a LAP-based regimen, LAP with capecitabine or TRA, had a
significantly reduced mortality rate (hazard ratio [HR], 0.42; range
0.27-0.64; p=0.0001), and that this treatment significantly improved
their OS (median 2233.0 versus 1199.0 days; p=0.0001) compared to
patients who received only TRA-based therapy. The presence of a bone
lesion at the time of diagnosis was associated with the patients’ survival
(HR, 1.96; range 1.28-3.00; p=0.002); however, the patients’ age, ER
status, and the presence of visceral lesions or BM at the diagnosis of
HER2+MBC did not. The patients who developed BM during anti-HER2
therapy had increased mortality due to their brain lesion, with a HR of
1.97 (1.26-3.10, p=0.003), however, the use of LAP significantly improved
their post-BM survival (median 622.0 days with LAP versus 287.0 days
without LAP; P<0.01).
Conclusions: According to our institutional review, LAP played a
significant role in the management of HER2+MBC in terms of improving
the patients’ survival. Various antibody-centered therapies will be the
mainstream of HER2+MBC management, however, we conclude LAP will
remain a useful treatment option.
PO61
ORAL VINORELBINE IN COMBINATION WITH TRASTUZUMAB AS
A FIRST LINE THERAPY OF METASTATIC OR LOCALLY ADVANCED
HER2-POSITIVE BREAST CANCER
Fadi Farhat3, Joseph Kattan2, Marwan Ghosn1
1Faculty of Medicine- Saint Joseph University, Hematology-Oncology,
Beirut, Lebanon; 2Hotel Dieu de France University Hospital, HematologyOncology, Beirut, Lebanon; 3Lebanese University, Hematology-Oncology,
Beirut, Lebanon
Background: The efficacy of vinorelbine (V) with trastuzumab (T) has
shown to be more than just additive in vitro. Moreover, V-T combination
proved to be an effective first line treatment for patients (pts) with
locally advanced (LA) or metastatic breast cancer (MBC) (HERNATA
phase III trial). Oral chemotherapy (CT), preferred by most of the pts,
represents a step forward in MBC management with a growing use in
Abstracts / The Breast 24 S3 (2015) S21–S75
S43
this setting. In order to improve pts’ comfort using the oral form of V, we
conducted a multicenter phase II study to investigate efficacy and safety
of the oral V-T (OVT) combination.
Methods: Main eligibility criteria: HER-2Neu positive disease (3+
IHC or FISH+), no adjuvant CT within the last 6 months and no prior
CT for MBC. Pts were treated with oral V (oV) 80 mg/m2 D1, D8, D15
(following first 3 administrations at 60 mg/m2 during the first cycle) for
a total of 8 cycles (1 cycle = 3 weeks); in combination with (T) 6 mg/
kg on D1 (loading dose, 8 mg/kg) every 3 weeks or 4 mg/kg (loading
dose, 6 mg/kg) weekly. Continuation and schedule of (T) were at
investigator’s discretion. Response was evaluated every 2 cycles using
RECIST 1.0.Primary endpoint: Objective response rate (ORR); secondary
EPs: Duration of response (DOR), progression free survival (PFS), overall
survival (OS), safety.
Results: In the full population (n=26), median age was 50.7 years
(range 31.3-80.7); median WHO PS 0 (range 0-1). 69% of pts were postmenopausal and 65% took prior (neo)adjuvant CT. Early stage treatment
consisted of a combination of anthracyclines (AC) and taxanes (TX) in
27% of pts. Overall 46% of the pts were pretreated by AC, 38.5% by TX.
Median disease free interval was 50.7 (95% CI [43.6-57.9]) months (m).
Most frequent metastatic sites were bone (61.5%), liver (50%) and lymph
nodes (42%). 73% of pts had 2 or more metastatic sites. A median of 8
oVT cycles were given (range: 3-12): 19% of oV doses were not escalated
to 80mg/m2 starting cycle 2. 92% of pts administered T every 3 weeks.
In the evaluable pts population, ORR was 56% (95% CI [34.9-75.6]),
including 3 complete responses (12%) and 11 partial (44%), 8 pts (32%)
had stable disease resulting in a clinical benefit [or disease control] rate
of 88 % (95% CI [68.8-97.5]). Median DOR was 7.1m (95% CI [3.9-10.2]).
At the time of the analysis, median PFS was 6.7m (95% CI [3.5-10]) and
median OS 27.9m (95% CI [17.4-38.3]). Treatment was generally well
tolerated with main observed grade 3-4 hematological toxicities being
neutropenia (46%) and anemia (4%). Grade 3-4 nausea-vomiting were
observed in 11.5% of pts.
Conclusion: Our results confirm the efficacy of OVT combination as a
first line treatment in Her2 Neu+ LA or MBC pts with an acceptable safety
profile. OVT optimizes the convenience of this CT regimen, especially for
the pts receiving T every 3 weeks.
distinct biological and clinical implications as compared to those
relapsing after prior treatment for early stage BC (recurrent disease). We
evaluated the patterns of care and clinical outcomes of HER2-positive
metastatic breast cancer (MBC) pts receiving first line trastuzumabbased therapy, according to the type of metastatic presentation.
Materials and Methods: This is a retrospective cohort study conducted
at 14 Italian centers within the GIM (Gruppo Italiano Mammella) group.
Consecutive pts undergoing first-line trastuzumab-based therapy were
eligible for the study. Analyses were performed according to the type of
presentation of metastatic disease (de novo or recurrent). Dichotomous
clinical outcomes were analyzed using logistic regression, and time-toevent outcomes using Cox proportional hazards models controlling for
relevant demographic, clinicopathologic and therapeutic characteristics.
All data were analyzed using Stata 12.3 (StataCorp LP).
Results: A total of 416 MBC pts (median age, range 42 – 63 years) were
included, 113 (27.2%) with de novo stage IV and 303 (72.8%) with recurrent
disease. A total of 64 (56.6%) and 186 pts (61.4%) had hormone-receptor
positive disease, respectively. Among pts with recurrent disease, 101
(33.3%) received prior trastuzumab-based therapy in the (neo)adjuvant
setting. In pts with de novo stage IV disease and in those with recurrent
disease, the following outcomes were observed, respectively: objective
response rate (complete response + partial response), 163 pts (67.1%) vs
72 pts (72.0%) (adjusted odds ratio [OR] = 0.90; 95% confidence intervals
[CI] 0.34–2.38; p = 0.833); clinical benefit rate (complete response
+ partial response + stable disease), 76 pts (76.0%) vs 187 pts (77.0%)
(adjusted OR = 1.21; 95% CI 0.40–3.64; p = 0.731); median progressionfree survival, 14.4 months vs 14.7 months (adjusted hazard ratio [HR] =
1.21; 95% CI 0.79–1.86; p = 0.380); median overall survival, 55.9 months
vs 49.0 months (adjusted HR = 1.26; 95% CI 0.71–2.23; p = 0.439).
Conclusions: The clinical outcomes of HER2-positive MBC pts with de
novo stage IV disease do not differ significantly from those of pts with
recurrent disease.
PO62
Uwe Güth2,3,5, Dorothy Huang5, Seraina Schmid4,1
Breast Center St. Gallen, Location Grabs, Grabs, Switzerland; 2Cantonal
Hospital Winterthur, Obstetrics & Gynecology, Winterthur, Switzerland;
3
Cantonal Hospital Winterthur, Breast Center “Senosuisse”, Winterthur,
Switzerland; 4Spital Grabs, Gynecology & Obstetrics, Grabs, Switzerland;
5
University Hospital Basel, Gynecology & Obstetrics, Basel, Switzerland
PO63
CURE IN METASTATIC BREAST CANCER: AN AGGRESSIVE APPROACH
DOES NOT APPEAR TO BE THE KEY TO THE BLACK BOX
1
FIRST LINE TRASTUZUMAB-BASED THERAPY IN HER2-POSITIVE
METASTATIC BREAST CANCER PATIENTS PRESENTING WITH DE NOVO
OR RECURRENT DISEASE: A MULTICENTER RETROSPECTIVE COHORT
STUDY
Matteo Lambertini6, Arlindo Ferreira4, Francesca Poggio6, Fabio Puglisi14,
Federico Sottotetti3, Elena Poletto14, Emma Pozzi3, Emanuela Risi10,
Antonella Lai1, Chiara Dellepiane5, Valentina Sini13, Serena Ziliani11,
Gabriele Minuti9, Donatella Grasso8, Sara Fancelli2, Silvia Mura12,
Paolo Pronzato6, Lucia Del Mastro7
1
Azienda Ospedaliera Universitaria di Sassari, Oncologia medica, Sassari,
Italy; 2Azienda Ospedaliera Universitaria Pisana, Polo Oncologico, Pisa,
Italy; 3Fondazione Maugeri IRCC, Unità Dipartimentale di Oncologia
Medica, Pavia, Italy; 4Hospital de Santa Maria, Instituto de Medicina
Molecular, Lisbon, Portugal; 5IRCCS AOU San Martino-IST, Department
of Medical Oncology, Clinica di Oncologia Medica, Genova, Italy; 6IRCCS
AOU San Martino-IST, Department of Medical Oncology, U.O. Oncologia
Medica 2, Genova, Italy; 7IRCCS AOU San Martino-IST, Department of
Medical Oncology, U.O. Sviluppo Terapie Innovative, Genova, Italy; 8IRCCS
San Matteo University Hospital Foundation, Medical Oncology, Pavia,
Italy; 9Istituto Tumori Toscano, Civil Hospital of Livorno, Department of
Medical Oncology, Livorno, Italy; 10Oncology Unit B; Sapienza University of
Rome, Department of Radiology, Oncology and Human Pathology, Rome,
Italy; 11Ospedale San Paolo, Oncologia Medica, Savona, Italy; 12Ospedale
Santissima Annunziata, Oncology Unit, Sassari, Italy; 13Sant’Andrea
Hospital, Sapienza University of Rome, Oncology Unit, Rome, Italy;
14
University Hospital, Department of Oncology, Udine, Italy
Background: Approximately 5-10% of breast cancer (BC) patients (pts)
have metastases at the time of diagnosis (de novo stage IV), suggesting
Introduction: It is a generally held belief that once a breast cancer
patient develops clinically detectable distant metastases, the disease
will lead inevitably to death. This tenet, however, has been repeatedly
called into question. Data from palliative chemotherapy trials showed
long-term complete remissions and thus provided level III evidence in
support of the hypothesis that distant metastatic breast cancer (MBC)
might be curable in up to 3% of the cases through a multidisciplinary
approach including combination chemotherapy regimens in selected
patients with limited metastases, usually young and in otherwise good
health. This study evaluates the rate of potentially cured patients in an
unselected consecutive cohort of patients with MBC.
Methods: We analyzed the data from 149 patients in whom MBC was
diagnosed from 1990-1999 at the University Women’s Hospital Basel,
Switzerland. Thirty patients (20.1%) had distant metastases at initial BC
diagnosis (primary metastatic disease), and 119 patients (79.9%) had
developed distant metastases over time, i.e. had secondary metastatic
disease. The median age at the time of MBC diagnosis was 62 years.
The criteria for being considered cured were: 1) the patients exhibited
long-term survival; and 2) had no evidence for disease: the initially
diagnosed metastatic lesions could no longer be detected.
Results: Five patients (3.4%) fulfilled the criteria for being cured. From
these, three patients had primary MBC. At the time of data analysis,
three patients were still alive (survival time after the diagnosis of
distant metastases: 17.6-21.2 years). Two elderly patients had died of
other diseases (survival time: 9.3/11.3 years). There were two peaks of
S44
Abstracts / The Breast 24 S3 (2015) S21–S75
age distribution at the time of MBC diagnosis: 41-57 years (n=3) and
76/79 years (n=2). Two patients had solitary metastatic lesions (bone,
n=2; lung, n=1), one patient had extensive bone metastases, and one
patient had multiple bony and pulmonary metastases. In only one of
the five cases did the patient receive chemotherapy in the supposed
palliative situation.
Discussion: There are patients who, despite the diagnosis of distant
metastases, may be considered cured of their disease; however, these
cases are rare. The long-term survivors in our study cohort comprised
a relatively heterogeneous group with regard to age at MBC diagnosis,
therapy and metastatic sites. The factors contributing to the quite rare
and felicitous case of long-term survival or even cure, can hardly be
evaluated systematically and remain a black box. It appears, however,
that aggressive chemotherapy-containing regimens, are not the key to
solving the mystery of this black box.
PO64
METRONOMIC CHEMOTHERAPY (CHT) COMBINATION OF
VINORELBINE (VRL) AND CAPECITABINE (CAPE) IN HER2- ADVANCED
BREAST CANCER (ABC) PATIENTS (PTS) DOES NOT IMPAIR GLOBAL
QOL. FIRST RESULTS OF THE VICTOR-2 STUDY
Marina Elena Cazzaniga7, Valter Torri1, Laura Cortesi8, Luca Clivio1,
Antonella Ferzi2, Filippo Giovanardi3, Mariangela Ciccarese6,
Palma Pugliese5, Silvia Della Torre4, Paolo Bidoli7
1
Mario Negri Institute, Oncology Unit, Milan, Italy; 2Ospedale Civile di
Legnano, Medical Oncology, Legnano, Italy; 3Ospedale di Guastalla, Medical
Oncology, Guastalla, Italy; 4Ospedale Guido Salvini, Medical Oncology,
Garbagnate, Italy; 5Ospedale Sant’Anna, Medical Oncology, Como, Italy;
6
Ospedale Vito Fazzi, Medical Oncology, Lecce, Italy; 7San Gerardo Hospital,
Medical Oncology Department, Monza, Italy; 8University of Modena and
Reggio Emilia, Medical Oncology and Haematology, Modena, Italy
Background: One of the main objectives in the treatment of ABC pts
is the preservation of QoL, also by limiting the CHT-related toxicities.
Metronomic CHT (mCHT) is a novel way of administering cancer drugs
at doses higher than the MTD with lower side effects. VRL and CAPE are
frequently burdened by grade 3-4 neutropenia, neuropathy and gastrointestinal toxicity. We recently published the results of the VICTOR-1
study, demonstrating that metronomic VRL-CAPE combination shows
a very low incidence of grade 3-4 toxicities. The phase II VICTOR-2
study was designed aiming to confirm the efficacy and safety data of
the previous trial, as well as the impact on QoL, by the use of QLQ-C30
questionnaire. Here we present for the first time data concerning
the impact of mCHT on Global QoL (items 29-30) and some of the
3-symptoms scales (items 14-17) during the treatment (baseline, T1=9
weeks, T2=18 weeks, T3=27 weeks).
Materials and Methods: The treatment consisted of VRL 40 mg thrice
a week + CAPE 500 mg tid, continuously, as 1st or further lines of
treatment. Main inclusion criteria were: Measurable or evaluable HER2disease, HR known status. To estimate the effect of mCHT on global
QoL and to assess a possible variation in QOL over time, the repeated
measure ANOVA was used.
Results: From September 2011 to April 2015, 84 pts entered the study;
56 pts (66.7%) completed the first pre-treatment questionnaire, 57.1%,
37.5% and 23.2% of them completed the second, third and fourth
questionnaire respectively, according to the above mentioned schedule.
Median age was 64 years (37-85). Baseline and after 27 weeks of
treatment mean values for Global Health Evaluation (item 29) were 4.9
and 5.0 (F Value=0.9), whereas mean values for Global QoL (item 30)
were 5.2 and 5.3 (F Value=0.7), indicating no deterioration of QoL during
the treatment. No deterioration on QoL for both 1st and 2nd line pts
(baseline: 4.8 vs 5.0; T3: 5.3 vs 4.8) was observed. The vast majority
of pts didn’t experience nausea (item 14: 61.5%), vomiting (item 15:
92.3%), constipation (item 16: 92.3%) or diarrhoea (item 17: 69.2%) after
27 weeks of uninterrupted treatment.
Conclusion: Metronomic combination of VRL and CAPE does not
affect QoL in advanced breast cancer pts and could be a valid option of
treatment both as 1-st or further lines of treatment.
PO65
PHASE II TRIAL OF METRONOMIC COMBINATION CHEMOTHERAPY
WITH ORAL REGIMEN IN HEAVILY PRETREATED METASTATIC BREAST
CANCER
Prasanna Rammohan
Madras Medical College, Medical Oncology, Chennai, Tamilnadu, India
Background: Metastatic breast cancer with prior anthracycline and
taxane exposure is difficult to treat in low resourceful countries like
India. We explored a combination of capecitabine and cyclophosphamide
as oral regimen in treatment of MBC as a palliative regimen to assess the
response rate, efficacy, toxicity profile (as primary endpoint) and time to
tumor progression (as secondary endpoint) in a phase 2 study.
Patients and Methods: The study was conducted after approval
from institutional ethical committee and in accordance with their
regulations. Written informed consent was obtained from all patients
prior to screening assessments or enrollment. The median age was
52 years (range 24-69). Performance status at baseline was ECOG 1 in
twenty one and 2 in nineteen patients. There were 23 postmenopausal
women. Hormone receptor (ER/PR) were positive in 24 patients, (ER
and PR) negative in 14 patients and unknown in 2 patients. HER2 status
was positive in 10 patients, negative in 24 patients and unknown in 6
patients. Thirty eight patients had been treated with chemotherapy
for metastatic disease and anthracycline exposed in 37 and taxane
chemotherapy in 39 patients. Fixed doses of capecitabine (1000 mg
twice daily) with oral cyclophosphamide (100 mg) were given on days
1-14, in a three weekly schedule. Flat dosing of the oral agents was
used as per published data indicating that the clearance of both drugs
is independent of body surface area. The treatment was repeated at a
3 week interval until disease progression.
Results: A complete response (CR) was obtained in two (5%) of 40
patients, and a partial response in 16 (40%) resulting in overall response
rate (ORR) of 45%. Twenty one patients had stable disease (SD) and
one had progressive disease (PD).When the treatment responses were
analyzed according to hormone receptor status (HR), ORR was 45.8%
including two CR and nine PR in 24 patients in HR positives, whereas
it was 42.8% including six PR in 14 patients in HR negatives. The ORR
in HER2 positive (10 patients) and negative (24 patients) was 20%
and 54.1% respectively. The most common (>20% patients) treatment
related adverse events were hand-foot syndrome (82.5%), fatigue
(57.5%), nausea (47.5%), elevated liver enzymes (35%), vomiting (27.5%),
mucositis (27.5%), diarrhea (22.5%), neutropenia (22.5%), anemia (22.5%).
Most treatment related adverse events were grade 1/2 in severity. None
of the patients had grade 3 adverse event and there were no patients
with febrile neutropenia or treatment related deaths. Grade 2 hand-foot
syndrome was observed in only 4 patients (12.1%).
Conclusion: In resource limited countries like India, metronomic
chemotherapy is an attractive option in anthracycline/taxane pretreated
advanced breast cancer patients because of low cost, good toleratance,
ease of administration and sound therapeutic efficacy.
PO66
NEOADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED BREAST
CANCER; A SOLUTION TO AVOID MASTECTOMY
Ahmed Tarek Awad1, Mahmoud Ahmed Elhussini1, Gamal El-Hussieny2,
Ahmed M. Basha1
1
Alexandria Faculty of Medicine, Surgical Oncology Unit, Alexandria,
Egypt; 2Alexandria Faculty of Medicine, Medical Oncology and Nuclear
Medicine, Alexandria, Egypt
We represent a series of 326 cases with locally advanced breast cancer
in whom the initial decision of surgery was mastectomy or some sort of
advanced oncoplastic technique e.g. partial volume replacement by mini
LD flap due to the tumor/breast ratio. After excluding any metastatic
foci, all patients were offered neoadjuvant chemotherapy. A radioopaque hydro-marker was inserted in the center of the lesion guided by
Abstracts / The Breast 24 S3 (2015) S21–S75
ultrasound. Patients were followed up by the surgical team every two
cycles. Follow up mammogram was done 3 weeks after the last cycle.
(MRI was done in some cases). Patients’ clinical response varied between
no clinical response, partial response and complete clinical response. No
patients showed progression on chemotherapy in our series. Decision
of surgery changed in 85% of the patients either from MRM to level I
or level II oncoplastic techniques or from level II to level I oncoplastic
technique. In 15% of the patients, the decision did not change either due
to inadequate response or due to the patients changed their mind to
MRM while receiving neoadjuvant chemotherapy. All patients received
postoperative radiotherapy. Follow up ranged from 6-30 months with
local recurrence in 3 cases (1 of them in the MRM group) and no distant
metastasis up till now.
PO67
NEO-ADJUVANT HORMONAL THERAPY FOR LOCALLY ADVANCED
BREAST CANCER
Lika Katselashvili, Margarita Katcharava, Sophio Kobakhidze
Research Institute of Clinical Medicine, Department of Oncology, Tbilisi,
Georgia
Background: In contrast to neoadjuvant chemotherapy (NAC), neoadjuvant endocrine therapy (NAE) is well tolerated, with very few
patients having to discontinue the treatment because of side effects, but
it cannot yet be considered similar to chemotherapy, which remains the
standard treatment.
Methods: We assessed retrospectively 778 patients with primary
breast cancer who underwent surgical resection after neo-adjuvant
treatment between 2003 and 2013 (a median age 54 years, range 2979 years). 576 patients (74%) had hormone-receptor positive tumor
and 98 patients (17%) had HER2 positive tumor. 144 patients with
large or locally advanced hormone receptor (+)/HER2 (-) breast cancer
received neoadjuvant treatment followed by surgery. 92 patients
of them received four cycles (c) of FEC 100 (epirubicin 100 mg/m2 +
5-fluorouracil and cyclophosphamide 500 mg/m2) followed by 4 cycles
of docetaxel (75 mg/m2) every 3 weeks for the NAC treatment regimen,
while letrozole was administered for 6 months for the postmenopausal
52 patients in the NAE treatment protocol.
Results: The hormone status was decreased by both NAC and NAE (from
53% to 30% and from 63% to 11%, respectively). ER (P=0.0327) and PR
(P=0.0019) were statistically decreased after NAE compared to NAC group.
The response rates by RECIST in the NAC- and NAE-treated patients were
0/32/57/11 and 0/48/46/6 (PD/SD/PR/CR%), respectively. The pathological
complete response rate was 11% after NAC and 6% after NAE.
Conclusion: Neoadjuvant endocrine therapy is a safe and feasible
option. Both of the NAC and NAE treatment protocols caused a decrease
in the tumor size. It does not constitute a standard treatment but could
have potential for elderly women with operable, hormonosensitive,
well differentiated and slowly progressing (SBR I) tumor or for patients
with lobular MSBR 1 carcinoma (low chemosensitivity). Patients with an
estrogen receptor Allred score of 6 and over are more likely to respond
and gain a clinical benefit.
PO68
TRIPLE NEGATIVE BREAST CANCER - NEOADJUVANT CHEMOTHERAPY
RESPONSE EVALUATION WITH TAXANE/ANTHRACYCLINE
PROTOCOL - SINGLE CENTRE 5 YEARS EXPERIENCE
Judy Vicente de Paulo, Ana Catarino, Bruno Gonçalves, Mónica Mariano,
Sofia Broco, Ana Pais, Isabel Pazos, Pedro Madeira, António Pêgo,
Teresa Carvalho, Gabriela Sousa, Helena Gervásio
Portuguese Institute of Oncology, Medical Oncology Department, Coimbra,
Portugal
Introduction: Triple negative breast cancer (TNBC), is one of the most
aggressive, therapeutic-resistant and metastatic breast cancer subtypes.
S45
Current therapeutic approaches do not distinguish the basal phenotype,
however TNBC is a heterogeneous group, with a high rate of complete
pathological response to neoadjuvant chemotherapy (NACT), therefore
this breast cancer subtype is source of intense debate and therapeutic
dilemma. Our institutional protocol consists in 4 cycles of docetaxel and
4 cycles of docetaxel in combination with epirubicin. The aim of our
work was to evaluate the results of the application of our Institutional
protocol.
Methods: We evaluated retrospectively the medical records of patients
with locally advanced TNBC with immunohistochemical diagnosis
in our Institute that had underwent NACT from 1 January 2009 to 31
December 2012. They were categorized in 3 subgroups according to
the degree of pathological response to NACT: If pathological complete
response (CPR), residual disease (RD) or “no answer” (considered if
there was a reduction of tumor size <50% or progression). We evaluated
demographic and clinical characteristics of the population and tumor
characteristics (grade, TNM staging and Ki 67). Multivariate statistical
analysis, including survival data, was performed using the SPSS v.22
program.
Results: A population of 68 female patients with a median age of 51.5
years were analyzed (31-76 years). Globally the population had a mean
survival of 58.13 ± 2.82 months (with a mortality rate of 25%). They
were divided into 3 subgroups according to the answer to NACT: 38.2%
(26 patients) with complete pathologic response (RPC), 25 patients
with residual disease (RD) and 17 patients non-responders (NR). The
RPC subgroup younger age of the 1st pregnancy, nulliparous 26.9%
(vs. 4% (RD) and 11% (NR) and 54 % premenopausal. The RPC subgroup
showed grade II/III in 100% CPR subgroup and Ki proliferation index was
67% vs. 55% 70.7 (RD) vs. 54% (NR) and correlated with response. The
basal phenotype(CK5/6+) did not correlate with the response to NACT
(p=0.479). Comparing survival among subgroups (long rank test) we
had statistically significant difference between overall survival rates at
3 years of 92% for RPC subgroup, 88% in RD and 37% in NR (p<0.001).
Conclusions: The neoadjuvant chemotherapy protocol using docetaxel /
docetaxel+epirubicin showed an complete pathological response rate of
38,2%. The basal phenotype did not correlate with the response pattern.
Despite being an retrospective evaluation, we observe the heterogeneity
of the TNBC patients, reflecting its therapeutical challenge and the need
for further studies in order to subcategorize the TNBC and its targeted
therapeutics.
PO69
BRACHIAL PLEXOPATHY IN METASTATIC BREAST CANCER: A REVIEW
OF PATIENT CHARACTERISTICS AND DIAGNOSIS IN AN IRISH
TERTIARY REFERRAL CENTRE
Connor O’Leary3, Niamh O’Donoghue3, Emily Harrold3, Claire Brady3,
Rachel Collins3, Louise Kelly1, Jennifer Gilmore4, Brian McNamara2,
Deirdre O’Mahony3, Seamus O’Reilly3
1
Cork Univeristy Hospital, Department of Surgery, Cork, Ireland; 2Cork
Univeristy Hospital, Department of Neurophysiology, Cork, Ireland; 3Cork
University Hospital, Department of Medical Oncology, Cork, Ireland; 4Cork
University Hospital, Department of Radiation Oncology, Cork, Ireland
Background: The brachial plexus is a complex network of nerves
formed from the spinal nerves C5 -T1. Brachial plexopathy is a condition
characterised by motor and sensory dysfunction affecting these
nerves. It is a recognised complication of breast cancer, resulting from
metastatic disease or fibrosis following previous regional surgery and/or
radiation. Metastatic disease accounts for the majority of cases. Clinical
differentiation between the two can be challenging as the physical
examination may be restricted by the effects of previous surgery and/
or radiation. In addition, there may in part be an overlap between the
symptoms of recurrence and previous treatment. Symptoms indicating
the need for imaging include pain, neurological deficit or muscle
atrophy. A review of the literature demonstrated the use of multiple
forms of imaging with varying degrees of reliability.
Methods: Patients with a new diagnosis of brachial plexopathy
secondary to metastatic breast cancer were indentified retrospectively
S46
Abstracts / The Breast 24 S3 (2015) S21–S75
from local records in a 3 year period. Information was collected on
patient age, tumour hormone receptor status and timeframes to
diagnosis of brachial plexopathy. The modalities used to confirm a
diagnosis of brachial plexopathy were analysed.
Results: 7 patients with metastatic breast cancer developed brachial
plexopathy in a 3 year period. The median age at presentation was 62
years. 5 patients were found to have hormone receptor positive tumours
and 2 patients had hormone insensitive tumours. The time interval to
the development of brachial plexopathy in the hormone sensitive group
varied from 9-24 years; median of 17 years. The 2 patients with hormone
insensitive tumours developed brachial plexopathy within a much
shorter timeframe; 2 and 4 years respectively. All patients underwent
magnetic resonance imaging (MRI) to visualise the brachial plexus. In
4 patients, this was sufficient to confirm brachial plexus involvement
by tumour. 3 of the patients required further investigation due to
equivocal findings on MRI. In these cases one or more further modality
was required, including positron emission tomography/computed
tomography (PET/CT) and nerve conduction studies.
Conclusion: Brachial plexopathy is uncommon. It is an important
differential diagnosis if new symptoms develop in the upper limb. The
condition should be considered even if the history of breast cancer
is remote, especially if the patient’s original tumour was hormone
sensitive. MRI allows for excellent visualisation of the brachial plexus
and improved soft tissue resolution. However, our findings suggest the
sensitivity of MRI for this condition is not reliable. MRI combined with
PET/CT and/or nerve conduction studies offers higher diagnostic yield
and improves specificity.
PO70
ESTROGEN RECEPTOR AS A NEGATIVE PREDICTOR OF COMPLETE
PATHOLOGICAL RESPONSE IN HER2 POSITIVE LOCALLY ADVANCED
BREAST CANCER
Rita Canario2, Jorge Cruz2, João Casalta-Lopes1, Bruno Gonçalves2,
Mónica Mariano2, Sofia Broco2, Ana Pais2, Isabel Pazos2,
Teresa Carvalho2, António Pego2, Pedro Madeira2, Gabriela Sousa2,
Helena Gervásio2
1
Centro Hospitalar e Universitário de Coimbra, Radioterapia, Coimbra,
Portugal; 2Instituto Português de Oncologia de Coimbra Francisco Gentil,
Medical Oncology Department, Coimbra, Portugal
Background: The addition of trastuzumab to standard neoadjuvant
chemotherapy increases the likelihood of achieving a pathological
complete response (pCR) in locally advanced HER2 positive (HER2+)
breast cancer. However, controversy remains regarding the subtypes
which might benefit the most of this treatment. The aim of our study
was to identify predictors of pCR in these groups of patients.
Methods: Retrospective analysis of a consecutive series of cases with
stage III HER2+ breast cancer treated with neoadjuvant chemotherapy
and trastuzumab in a single Portuguese cancer center from June
2008 until December 2014. Data extracted from clinical files included
demographics, grade, estrogen receptors (ER), progesterone receptors
(PR) and Ki67 status from the original tumour sample. pCR was defined
as the absence of invasive or in situ neoplasm in the breast and axilla.
Univariate analysis was performed using Mann-Whitney test and
multivariate analysis was conducted with logistic regression. Survival
was assessed using Kaplan-Meier’s method.
Results: A total of 65 individuals were included, median age 52.5 (21-75).
Groups were balanced according to the molecular subtype, with 44.6%
Her2 pure and 55.4% luminal Her2. The median ER expression was 10%
(0-100%), PR 0% (0-100%) and Ki67 35%. The overall pCR rate was 50.8%,
significantly higher in the HER2 pure group (72.4% vs 33.3%, p=0.02).
ER expression was significantly lower in patients with pCR (median
0% vs. 60%, p=0.002), with no differences in PR or Ki67 expression. ER
has maintained prognostic value in multivariate analysis (HR= 1.034,
[1.012; 1.057], p=0.003). 5-year progression-free survival (PFS) and
overall survival (OS) were 81.3% and 91.2%, respectively. There were no
differences in PFS or OS between responders and non-responders.
Conclusion: The extent of ER expression constitutes an independent
negative predictor for pCR, corresponding in our data to an increase in
risk of 3.4% for each unitary increase in percentage of ER expression.
This data adds to the growing evidence that ER positive patients might
be over treated with chemotherapy. Further studies are needed to
establish a new standard of care.
PO71
MONITORING THERAPY RESPONSE IN METASTATIC BREAST CANCER
USING TUMOUR MARKERS CA15-3 AND TPS
Marie Sundquist1, Joakim Nilsson1, Göran Tejler2
1
County Hospitals, Breast Unit Surgery, Kalmar, Sweden; 2County Hospitals,
Surgery, Västervik, Sweden
Background: Metastatic breast cancer (MBC) is with few exceptions
mortal. Many patients can however survive for many years receiving
chemotherapy and/or targeted treatments. Response time to a single
therapy varies from months to several years. Many treatments are
associated with severe side effects. To assess when the disease no longer
responds to a particular treatment is important in order to spare the
patient unnecessary side effects and be able to switch to a new regimen.
Sometimes standard radiology fails in detecting progression.
Aim: To assess the role of serum tumour marker CA 15-3 and TPS in
monitoring therapy response in MBC.
Material and Methods: Approx. 200 pts treated for metastatic breast
cancer in Kalmar County 1995 to 2015 were retrospectively investigated.
The levels of CA15-3 and TPS were compared to clinical outcome and
pathological parameters. Their usefulness was graded according to how
well the tumour marker values correlated to clinical status. Information
on HER2, steroid receptor status and metastatic site were also collected
and used for analysis.
Results: Increased levels of CA 15-3 were found in 64 % and of TPS in 63 %
of pts at the time of diagnosis of distant metastasis. ER positive tumours
had elevated CA 15-3 levels more often than HER2 positive/ER negative
tumours. Metastasis in bone and liver were more often associated with
elevation of both markers than sole pulmonary metastasis. In 23 % of
patients CA15-3 and in 20 % TPS increased or decreased significantly
before any change in tumour volume could be detected by standard
radiology. Lead time varied from 2 to 11 months. The most increased
lead time occurred in hepatic metastasis and in grade 1 and 2 tumours.
Conclusion: The serum tumour markers CA15-3 and TPS are useful in
monitoring therapy response and disease progression in metastatic
breast cancer.
PO72
THERAPEUTIC EFFECT PREDICTION BASED ON BIOMARKERS IN THE
PLEURAL EFFUSION SPECIMENS OF BREAST CANCER PATIENTS
Rikiya Nakamura1, Naohito Yamamoto1, Nobumitu Shiina1,
Toshiko Miyaki1, Dai Ikebe2, Makiko Itami2
1
Chiba Cancer Center Hospital, Breast Surgery, Chuou Chiba, Japan; 2Chiba
Cancer Center Hospital, Diagnositic Pathology, Chiba, Japan
Purpose: The aim of this study was to investigate the possibility of
therapeutic effect prediction of endocrine therapy or angiogenesis
inhibitors against metastatic breast cancer.
Methods: The subjects were 32 cases of advanced or recurrent
breast cancer who underwent pleural effusion aspiration suspected
carcinomatous pleurisy from February 2014 to April 2015. Cell block
section from 32 serous pleural effusion specimens were stained with
biomarker such as ER, HER2 and VEGF-A. Expression of these biomarkers
investigated the possibility of a predictor for therapeutic effect on
endocrine therapy or angiogenesis inhibitor.
Results: Twenty eight specimens were confirmed metastatic
carcinomas from the breast and one specimen was from the primary
lung carcinoma. Three specimens were not confirmed adenocarcinoma
Abstracts / The Breast 24 S3 (2015) S21–S75
cells. Loss, increase, or no change in ER staining in primary tumour and
pleural effusion specimens was observed in 7, 0 and 21 cases (19 cases
were positive, 2 cases were negative), respectively. In two of these 19
cases with ER positive, endocrine therapy was performed. In one of
two patients, endocrine therapy achieved long stable disease. However,
endocrine therapies were ineffective in all cases of ER loss in pleural
effusion specimens. No discrepancy of HER2 expression from primary
tumours and pleural effusion specimens were confirmed. Positive
staining cell for VEGF-A was found to be present in 75% of pleural effusion
specimens (15 of 20 specimens). Eight pleural effusion specimens were
not available to VEGF-A staining because of a few carcinoma cells. In
2 of these 15 cases with VEGF-A positive, bevacizumab antiangiogenic
agents were administered. Therapeutic effects were confirmed in both
patients. However, these agents were administered in 2 of 5 cases with
VEGF-A negative and therapeutic effects were confirmed in one patient.
Conclusions: The results of this study emphasize the reliability of
immunohistochemistry in pleural effusion specimens. Therapeutic
effect prediction based on biomarkers in the pleural effusion specimens
of breast cancer patients may be promising in loss cases of ER staining.
PO73
OUTPATIENT CATUMAXOMAB THERAPY IN METASTATIC BREAST
CANCER PATIENTS SUFFERING FROM MALIGNANT EFFUSIONS DUE TO
PERITONEAL OR PLEURAL CARCINOMATOSIS: A SINGLE INSTITUTION
EXPERIENCE
Christian Martin Kurbacher1, Ann Tabea Kurbacher1, Susanne Herz1,
Katja Monreal1, Claudia Schweitzer1, Gabriele Kolberg1,
Jutta Anna Kurbacher2
1
Gynecologic Center Bonn-Friedensplatz, Gynecologic Oncology
Department, Bonn, Germany; 2Gynecologic Center Bonn-Friedensplatz,
General Gynecology and Obstetrics, Bonn, Germany
Background: Malignant effusions (ME) due to peritoneal (PC) or pleural
carcinomatosis (PLC) are frequent complications of advanced metastatic
breast cancer (MBC) indicating a worse prognosis. Many patients (pts)
wish to spend most of their remaining life span at home. Unfortunately,
specific therapeutic options for ME applicable to outpatients are limited
so far. The trifunctional antibody catumaxomab (CATU) is approved for
the treatment of malignant ascites related to epithelial tumors including
MBC. CATU can be safely given to carefully selected outpatients with PC
and even PLC due various carcinomas [Kurbacher et al. Proc ESMO 2014;
Proc IGCS 2014]. This retrospective analysis summarizes our single
institution experience with outpatient CATU therapy (Tx) for PC and PLC
in heavily pretreated MBC pts.
Methods: From our database, we identified 14 MBC pts (PC, n=7; PLC,
n=7) who received outpatient CATU Tx for symptomatic ME. Pts had
failed 3-11 prior systemic Tx (median: 5). 10 pts had invasive-lobular
carcinoma (all ER+, HER2-), 2 pts had HER2+ invasive-ductal carcinoma,
one of them ER+. In PC pts, Tx was planned to be given over a 14 d period
at 4 increasing doses (10 g, 20 g, 50 g, 150 g) using an indwelling
intraperitoneal (IP) catheder. 6 PCL pts received CATU as a single
intrapleural (IPL) instillation at 50 g. In the remainder presenting
with a permanent IPL catheder, CATU was administered according to
the IP protocol. Standard premedication comprised both non-steroidal
pain-killers and antiemetics. Adverse effects were scored according to
CTCAE 4.03. The puncture-free survival (PuFS) was calculated from start
of CATU until the next puncture, death or loss to follow-up whatever
occurred first. Overall survival (OS) was calculated from start from Tx
until death from any reason or loss to follow-up.
Results: CATU was generally well tolerated. Only one pt with PC required
secondary hospitalization due to toxicity (fever, infection). However,
only 2 PC pts received all 4 planned IP CATU instillations. The main
reason for Tx discontinuation and secondary hospitalization was rapid
progression in 4 pts. In contrast, all pts with PLC were treated as planned
and none of them required hospitalization following CATU. Secondary
puncture due to ME was necessary in 3 pts (PC, n=2; PLC, n=1). One pt
with PLC is still alive and free from puncture for 547 days. Pts with PLC
S47
compared favorably to PC pts in terms of both PuFS (112 vs 18 d, p=0.06)
and OS (118 vs 27 d, p=0.01).
Conclusions: Outpatient CATU is safe and feasible in careful1y selected
MBC pts with ME due PC or PLC. However, the degree of benefit was
remarkably lower in PC compared to PLC pts. IPL could be a valuable and
low-toxic option in MBC pts seeking for a specific outpatient Tx for PC.
PO74
WHICH IS MORE BENEFICIAL AS AN INITIAL THERAPY FOR THE FIRST
DISTANT METASTASIS OF BREAST CANCER: CHEMOTHERAPY OR
ENDOCRINE THERAPY FOR HORMONE RECEPTOR-POSITIVE, HUMAN
EPIDERMAL GROWTH FACTOR RECEPTOR 2-NEGATIVE BREAST
CANCER PATIENTS? A SINGLE-CENTER STUDY
Jun Yamamura, Kamigaki Shunji, Tsujie Masaki, Kimura Yutaka,
Osato Hiroki
Sakai City Hospital, Breast Surgery Department, Sakai City, Japan
Background: Patients with hormone receptor-positive (HR+), human
epidermal growth factor receptor 2-negative (HER2-) breast cancer may
experience distant metastasis after adjuvant therapy. After diagnosis
of the first distant metastasis, these patients will receive either
chemotherapy (CT) or endocrine therapy (ET). However it is still unclear
which therapy has a more beneficial effect in the prognosis. We studied
the outcomes and survival of these patients who received either CT or
ET after diagnosis of the first distant metastasis.
Methods: This is a chart review study of HR+/HER2- breast cancer
patients who received the standard of care and subsequently experienced
distant metastasis after diagnosis of primary breast cancer between Jan
1999 and Dec 2011 in Sakai City Hospital, Japan. We assessed objective
response rate, progression free survival (PFS) and overall survival (OS)
after an initial therapy for the first distant metastasis.
Results: We studied 92 patients with HR+/HER2- breast cancer who
experienced distant metastasis after adjuvant therapy. Of these patients,
32 (35%) patients were treated with CT as an initial treatment for the
first distant metastasis, 57 (62%) were treated with ET, and 3 (3%) had
no treatment. Disease characteristics were well balanced in between the
CT and ET groups. The response rate was 47% in the CT group, and 12%
in the ET group (p=0.001). Median PFS was 6.6 months in the CT group,
and 8.2 months in the ET group (HR: 0.919, 95% CI 0.501-1.686, p=0.784).
Median OS was 2.1 years in the CT group, and 2.3 years in the ET group
(HR: 0.676, 95% CI 0.389-1.744, p=0.160).
Conclusion: CT might have a better response as an initial treatment for
distant metastasis. However our retrospective study could not provide
clarification verifying which initial therapy was more beneficial for
HR+/HER2- patients. It would have been better to administer more
moderate treatments appropriate for the patients regardless of CT or ET.
If future efforts were conducted with a larger spectrum of patients and
treatment analysis, results might be more conclusive.
PO75
THE CTPET/MDST RATIO: AN INTRODUCTION OF A QUANTITATIVE
MEASURE OF EFFECTIVE PALLIATIVE ENDOCRINE THERAPY IN
METASTATIC BREAST CANCER
Uwe Güth2,3,6, Andreas Schötzau4, Dorothy Huang6, Seraina Schmid5,1
1
Breast Center St. Gallen, Grabs, Switzerland; 2Cantonal Hospital
Winterthur, Breast center “Senosuisse”, Winterthur, Switzerland; 3Cantonal
Hospital Winterthur, Obstetrics & Gynecology, Winterthur, Switzerland;
4
Eudox Institute for Biomathematics, c/o, Basel, Switzerland; 5Spital Grabs,
Gynecology & Obstetrics, Grabs, Switzerland; 6University Hospital Basel,
Gynecology & Obstetrics, Basel, Switzerland
Introduction: This study provides real-world clinical evidence
regarding endocrine therapy (ET) in the overall course of metastatic
disease in hormone receptor (HR)-positive breast cancer (BC). In this
study, we introduced a quantitative measure of how long the metastatic
S48
Abstracts / The Breast 24 S3 (2015) S21–S75
disease course can be controlled by endocrine agents in relation to the
overall palliative survival time.
Methods: From a non-selected cohort of women who were treated at
the University Women’s Hospital Basel for newly diagnosed BC in a 20year period (1990-2009), we analyzed 205 consecutive patients who
had or developed distant metastatic HR-positive disease over a 15-year
period (1997-2011). In order to give a quantitative description of the
overall duration of ET in relation to palliative survival time, we evaluated
the “cumulative time of palliative endocrine therapy” (CTPET). When
patients received several lines of ET, the duration of each line was added
to the CTPET. In a further step, we calculated the ratio between CTPET
and metastatic disease survival time (MDS). This ratio describes the
percentage of the patient’s survival time after diagnosis of metastatic
disease during which endocrine therapy had been administered as
the only systemic therapy. The CTPET/MDS ratio was only analyzed in
patients who had a survival time of at least nine months (n=145, 87.9%).
Results: 165 patients (80.5%) received ET as a part of palliative care.
The median number of therapy lines was two (range: 1-7). The median
duration was 18 months (range 0.5-133 months). The median metastatic
disease survival (MDS) was 34 months (range: 1-137 months). The
median CTPET/MDS ratio was 70.6 (range 2.1-100). Patients who were
therapy-naïve had a higher ratio (p=0.002) than those who were not.
Discussion: ET is widely applied in palliative cases of HR-positive BC.
Only in approximately 20% of cases was this option not carried out. In
particular, patients who were ET-naïve responded well to palliative ET.
If metastatic BC could be stabilized in such a way that the palliative
situation could be viewed as a chronic disease process, then effective
ET formed an important cornerstone in their management; in general,
the longer disease progression was suppressed by ET, the longer the
MDS. With this study, we introduced the CTPET/MDS ratio into the
literature. In our opinion, this is a promising quantitative measure of
how long the metastatic disease course can be controlled by agents
which offer, compared to chemotherapy, many advantages (safety,
efficacy, convenience, favorable side-effect profile). After excluding
those patients with rapidly progressive courses, our data showed that
the disease was controlled and stabilized for about 70% of the entire
palliative course with ET alone.
PO76
THERAPEUTIC STRATEGY FOR RECURRENT HER2-POSITIVE BREAST
CANCER PATIENTS
Akimasa Nishimura, Takashi Nishi, Akiko Igawa, Kensuke Okano,
Eri Yoshida, Kenichi Hakamada
Hirosaki University, Surgery, Hirosaki, Japan
Introduction: In 2014, the American Society of Clinical Oncology
published their guideline for systemic therapy for patients with
advanced human epidermal growth factor receptor 2(HER2)–positive
breast cancer. They recommend trastuzumab, pertuzumab and taxane
for first-line treatment and T-DM1 for second-line treatment. They
described that clinicians might offer first-line endocrine therapy alone
in special circumstances. In this study, we clarify what is the best
indication for HER2-positive and estrogen receptor-positive patients to
receive endocrine therapy as the first-line therapy.
Patients and Methods: We performed an operation on 732 patients
for breast carcinomas at our hospital from January 2002 to December
2013. We reviewed their medical records and included recurrent HER2positive patients into this study. We examined clinicopathological
factors of the patients such as ER status, the first recurrent site and the
number of involved organs. We calculated survival rates using KaplanMeier method and compared the differences using log-rank tests.
Result: 14 HER2-positive breast carcinoma patients had a relapse. The
median survival time after the relapse was 34 months. The survival time
of the patients with one organ involved and with two or more organs
involved was not reached and15 months, respectively. The patients
with one organ involved survived significantly longer than the others
(p=0.003). As the first-line therapy, 7 patients received an anti-HER2
targeted drug and 3 patients received no anti-HER2 drug. The time to
receive the first-line therapy was 8.4 (range: 1–15) months for patients
with an anti-HER2 drug, and 16.0 (range: 2–30) months, respectively.
Conclusion: We concluded that we could offer endocrine therapy as
the first-line therapy to HER2-positive and estrogen receptor-positive
patients with one organ involvement.
P077
LOCALLY ADVANCED BREAST CANCER IN YOUNG FEMALE. THE
EGYPTIAN NATIONAL CANCER INSTITUTE EXPERIENCE
Amany Helal2, Amira Darwish2, Nelly Alieldin3, Lydia Soliaman1
1
Faculty of Medicine, Beni Suef University, Medical Oncology, Beni
Suef, Egypt; 2National Cancer Institute, Medical Oncology, Cairo, Egypt;
3
National Cancer Institute, Biostatistics & Epidemiology, Cairo, Egypt
Background: The objective of this study is to analyze the clinicopathologic characteristics, treatment and outcome of young women
below 35 years old with locally advanced breast cancer (LABC) who
were treated at national cancer institute, Cairo University.
Patients and Methods: A retrospective analysis was conducted based
on medical records from consecutive young females patients below 35
years old with (LABC) treated during 2008-2010 at NCI. The patients’
records were identified and their pathological and clinical data were
retrieved.
Results: Of the 458 young patients diagnosed with breast cancer, 160
patients (35%) presented with LABC. Patient’s median age was 32 years.
Only 9.4 % of patients were single, 15.6% were nulliparous, while 46.8%
had ≥ 3 children. Oral contraception was used by 9%. Median tumor size
at diagnosis was 4.5 cm (range: 1-15cm). Histology showed invasive
duct carcinoma in 85% and invasive lobular carcinoma in 4%. Estrogen
receptors were positive in 74.8% and progesterone receptors were
positive in 67.4%. In 26.3% HER2 was over-expressed. Thirty percent of
the patients received preoperative chemotherapy (CT). Primary CT was
anthracycline- based in 89.6% and anthracycline followed by taxanes
in 10.4%, 17.2% underwent conservative breast surgery, while 87% had
modified radical mastectomy. Ninety percent of patients received
adjuvant CT, 91.8% received adjuvant radiotherapy and and patients
with hormone receptors positive received adjuvant hormonal therapy.
At a median follow-up of 25 months (range: 1-70), 56.9% of the patients
had no evidence of disease. Two patients (1.25%) died with no evidence
of recurrence. In 41.9% of patients the tumor recurred, 4.4% of them had
only local recurrence, 35% had distant metastasis and 2.5% had both
local and distant metastasis.
Conclusion: In our institute almost 1/3 of women under 35 years with
breast cancer had locally advanced disease in their first presentation.
Local recurrence rate was low (6.9%) however 37.5% of patients
developed distant metastases. So further studies are recommended to
increase awareness to early tumor detection and to optimize systemic
treatment strategies.
PO78
ELDERLY WOMEN AND BREAST CANCER: CHARACTERIZATION OF
TREATMENT PRACTICES
Diana Freitas, Ana Marques, Joana Cunha, Luísa Queiróz,
Catarina Portela, Rui Nabiço
Hospital de Braga, Medical Oncology Department, Braga, Portugal
Introduction: In Europe, incidence for women 70 years or older varied
from 100 to 350/100 000/year. In a general, elderly women with breast
cancer are considered underdiagnosed and undertreated, with adversely
affects in their overall survival.
Objective: Characterize therapeutic options in elderly patients and
understand the choices in those patients.
Material and Methods: Retrospective study of 25 women with the
diagnostic of locally advanced breast cancer (LABC) with ≥ 70 years old
in Braga Hospital within the years 2007-2008.
Abstracts / The Breast 24 S3 (2015) S21–S75
Results: The average age was 77 years old (70-88) Regarding histology
type, 88% (N=22) were ductal carcinoma and 4% (N=1) with lobular
carcinoma, lobular and ductal carcinoma and a papillary carcinoma,
respectively. Most patients had a tumor grade 2 (60%, N=15) and 20%
grade 1 (N=5). Median tumor size with 12 mm (25-100). Fifty-two
percent (N=13) belongs to stage II. About 92% expressed estrogens
receptors and 80% progesterone receptors. Her2 was positive in eleven
patients (44%) and unknown/doubtful in 3 patients (12%). The primary
treatment was surgery in 80% (N=20), chemotherapy (CT) in 12% (N=3)
and hormone therapy (HT) in 8% (N=2). Regarding surgery, mastectomy
with axillary lymph node dissection was done in 72% (N=18), mastectomy
with sentinel lymph node biopsy (SLNB) in 16% (N=4), 8% (N=2) simple
mastectomy and 4% (N=1) lumpectomy with SLNB. Adjuvant treatment
such CT, radiotherapy (RT) or HT were done in 36% (N=9), 68% (N=17)
and 88% (N=22), respectively. Relatively to CT, in 24% (N=6) was use CMF
(cyclophosphamide, methotrexate fluorouracil), FEC in 4% (N=1), FEC-T
(N=2, 8%), AC (4%, N=1), AC-T (4%, N=1). When we divided patients in
<80 years (N=13) and ≥80 years (N=12), the analysis in terms of primary
treatment reveals that patients ≥80 years were treated only with
surgery (83%) or HT (16.7%). In the total 11 patients that received CT,
only one patient had more than 80 years. RT was use in 76.9% (N=10)
in <80 years versus 58.3% in ≥80 years. The major reasons to choose not
to do standard treatment, when described, were performance status
and comorbidities, mostly cardiac pathology. In the total of 25 patients,
8% (N=2) are dead without disease evidence and 12% (N=3) are dead
with disease evidence. Median overall survival was 70 months and the 5
years survival rates was 87.05%.
Conclusion: Studies shows that elderly patients do not receive the
standard treatment. Our study corroborates that treatments like CT
or RT is less used in older patients. Physiological age, estimated life
expectancy, risks, benefits, treatment tolerance, patient preference
and potential barriers should be considered in management for older
individuals. Geriatric assessment is crucial to try to make the best
decision.
PO79
ELDERLY METASTATIC BREAST CANCER AT DIAGNOSIS: A SINGLE
INSTITUTION EXPERIENCE
Amanda Nobre Carvalho, Beatriz Gosalbez, Carlos Reis, Irene Furtado
Algarve Hospital Centre, Medical Oncology Department, Faro, Portugal
Background: One to five percent of women with breast cancer have
metastatic disease at diagnosis. In elderly population the goals of
treatment are to reduce symptoms when present and to provide the
patient with the best quality of life for as long as possible.
Methods: An observational and retrospective study of metastatic breast
cancer at presentation in women aged 65 years and older diagnosed from
January 2008 to December 2014. Demographic data, tumor characteristics,
treatment options and overall survival were analyzed using SPSS® 2.20
(Statistical Package for the Social Sciences, SPSS Inc., Chicago, IL).
Results: In the past seven years a total of 487 cases of breast cancer
in elderly patients were diagnosed, 25 women of them (5.1%) had
metastases at presentation (stage IV). Median age was 76 years (range
63 to 83). Hormonal receptors (ER and/or PR) were positive in 19 (76%)
and HER2 was positive in 6 (24%); there were 3 “triple negative” tumors
(12%). The most frequent organs for metastases were the bone in 13
patients (50,2%) and the liver in 9 (36%). Metastases in multiple organs
were found in 8 patients (32%). The performance status was 2 in 18
patients (72%). Treatment options were hormonal therapy in 17 (68.0%);
chemotherapy in 7 (28%); radiotherapy in 7 (28%) - mainly for bone
metastases; bifosfanates in 11 (44%) patients. Median overall survival
was 22.1 months [95% CI (7.5-36.7)].
Conclusion: The treatment of metastatic breast cancer in elderly
population is a challenge because the lack of evidence on this setting.
The hormonal therapy is a good option with evident clinical benefits.
In our population the median overall survival not reached with the
hormonal treatment, for those with hormonal receptors positive and
median follow-up time was 20,1 months (range 4.2 to 62.4).
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PO80
ELEVATED NEUTROPHIL TO LYMPHOCYTE RATIO PREDICTS WORSE
SURVIVAL OUTCOME AFTER RECURRENCE FOR PATIENTS WITH
TRIPLE NEGATIVE BREAST CANCER
Toshiaki Iwase1, Takafumi Sangai1, Masahiro Sakakibara1,
Takeshi Nagashima1, Shouko Hayama1, Masaru Miyazaki2
1
Chiba University Hospital, Breast and Thyroid Surgery, Chiba City, Chiba,
Japan; 2Chiba University Hospital, General Surgery, Chiba City, Chiba,
Japan
Background: Cancer induced chronic inflammation shortens overall
survival for metastatic breast cancer patients by reducing muscle mass
and prompting cachexia. Recent studies show that obesity plays a major
role in causing chronic inflammation by producing several inflammatory
cytokines. On the other hand, there is limited research focusing on the
effect of obesity in recurrent breast cancer treatments. Since a long time
ago, neutrophil to lymphocyte ratio (N/L ratio) has been utilized for
evaluating inflammation and many reports confirmed that substitution
value. Therefore, we set out to clarify the impact of obesity related
inflammation by N/L ratio in recurrent breast cancer treatment.
Patients and Methods: From January 2005 to December 2014, 93
patients with recurrent breast cancer after surgery were included.
World Health Organization body mass index (BMI) classification was
used for evaluating the degree of obesity (underweight: <18.5 kg/m2,
normal: 18.5 ≤ BMI <25 kg/m2, overweight: 25 ≤ BMI < 30 kg/m2, obese:
≥30 kg/m2). Muscle mass amount was also analyzed. Lumber skeletal
muscle index (LSMI, cm2/m2) was generated by standardizing each
patient’s muscle area (m2) at the third lumber vertebrae level in axial
CT data. Less than 50m2 in LSMI was defined as pre-sarcopenia. N/L ratio
was calculated from the laboratory data, and more than 3.0 was defined
as high N/L group. Overall survival after recurrence (OS) was set as the
endpoint of this present study.
Results: Patient background showed there were 20 overweight
patients and 2 obese patients. Twenty-eight cases had pre-sarcopenia.
In univariate analysis, N/L ratio had no significant differences among
BMI categories. However, triple negative (TN) type demonstrated
significantly high N/L ratio compared to other subtypes (p < 0.05). LMSI
had significant negative correlation to N/L ratio (p < 0.05). In survival
analysis, overweight/obese group showed significantly shorter OS (p <
0.05). High N/L ratio group also showed similar results (p < 0.05). When
stratified by intrinsic subtypes, TN type demonstrated significantly
shorter OS (p < 0.05). Additionally, overweight/obese groups in TN type
had notably shorter OS (p < 0.05). In multivariate analysis, subtype and
N/L ratio were independently related to OS (Hazard ratio: 3.3 in TN type,
2.9 in High NL ratio group).
Conclusion: Present study did not show any significant relationship
between obesity and chronic inflammation in recurrent breast cancer
setting. On the contrary, intrinsic subtype was significantly related to
inflammation, leading to pre-sarcopenia and worse OS. Whether obesity
promotes inflammation in TN type needs more investigation.
PO81
COMPLIANCE AND PERSISTENCE TO PALLIATIVE ENDOCRINE
THERAPY IN METASTATIC BREAST CANCER
Uwe Güth2,3, Andreas Schötzau4, Dorothy Huang6, Seraina Schmid5,1
1
Breast Center St. Gallen, Spital Grabs, Grabs, Switzerland; 2Cantonal
Hospital Winterthur, Obstetrics & Gynecology, Winterthur, Switzerland;
3
Cantonal Hospital Winterthur, Breast Center “Senosuisse”, Winterthur,
Switzerland; 4Eudox Institute for Biomathematics, c/o, Basel, Switzerland;
5
Spital Grabs, Gynecology & Obstetrics, Grabs, Switzerland; 6University
Hospital Basel, Gynecology & Obstetrics, Basel, Switzerland
Introduction: This study provides real-world clinical evidence regarding compliance and persistence to palliative endocrine therapy (ET) in
breast cancer (BC) patients.
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Abstracts / The Breast 24 S3 (2015) S21–S75
Methods: From a non-selected cohort of women who were treated at
the University Women’s Hospital Basel for newly diagnosed BC in a 20year period (1990-2009), we analyzed 205 consecutive patients who
had or developed distant metastatic HR-positive disease over a 15-year
period (1997-2011). We defined “compliance” as the readiness to accept
a proposed drug; in other words, to accept starting ET. Non-persistence
to therapy is not simply the act of stopping medication, but rather
the manifestation of an intentional behavior. Thus, situations where
the discontinuation of therapy was not chosen but was mandatory, in
particular when patients had to stop therapy due to disease progression,
were not defined as being “non-persistent”.
Results: From the entire study cohort, 165 patients (80.5%) received ET
as a part of palliative care. Of the 169 cases in which ET was clearly
recommended, only three patients rejected the therapy, which
corresponded to a non-compliance rate of 1.8%. Out of the 165 women
who started ET, seven (4.3%) were non-persistent to the initiated
therapy and consciously stopped a still effective, ongoing therapy; out
of these, four (67.1%) did so due to therapy-related side effects and three
(42.9%) due to reasons such as lack of motivation/faith in therapy. Of the
patients who started palliative ET, the therapy-related side effects were
so severe in 14 patients (8.5%) that a modification of the therapy was
indicated. From these, one drug switch was made in 11 cases (78.6%),
two medication changes were necessary in 2 cases (14.3%) and the
medication was changed three times in one case (7.1%). Out of the 14
cases in which a drug switch was made, 11 patients (78.6%) continued
ET after therapy modification.
Discussion: Only very few patients were non-persistent to the initiated
ET and consciously stopped a still effective, ongoing ET. Low nonpersistence data suggests that most patients knew very well that ET in
the palliative situation could prolong survival with considerably little
effort on their part and with, compared to chemotherapy, a lower rate
of side effects. These side effects might not be tolerated in the adjuvant
situation to a certain extent (there are considerably higher nonpersistence rates reported in the literature in the adjuvant situation),
but may be well accepted in the palliative situation. The patients were
probably also well informed about the limited number of therapy lines
available to them and were thus less willing to try to change therapy due
to therapy-related side effects.
patients was 6.24 months with 42 patients (24.6%) on taxane-based and
39 patients (22.8%) on antracycline-based regimens, and of hormonal
therapy - 14.25 months with most frequent regimen of aromatase
inhibitor: 66 subjects (38.6%).
Conclusions: This study provides unique real life data on current clinical
management and outcomes in MBC patients in Bulgaria.
PO83
CURRENT STATUS OF THE MANAGEMENT OF ADVANCED RH+/HER2BREAST CANCER IN MOROCCO
Errihani Hassan2, Taleb Amina1, Mrabti Hind2, Elghissassi Ibrahim2,
Boutayeb Saber2, Narjiss Berrada2
1
Ibn Rochd, Dept. of Oncology, Casablanca, Morocco; 2National Institute of
Oncology, Medical Oncology Department, Rabat, Morocco
PO82
Background: The management of breast cancer in Morocco is done
by different specialists; medical oncologist, radiation oncologist and
sometimes by surgeon. The provision of care is not uniform and depends
on the physicians and sectors ( public versus private). Interdisciplinary
meeting are not well implemented in all cancer centers and local
recommendations are absent. The purpose of this work was to describe
the current situation in the management of advanced RH+/her2- breast
cancer in Morocco.
Materials and Methods: We realized a survey among 50 oncologists
(medical and radiation oncologist) working in different centers about
their management of RH+/Her2- advanced breast cancers.
Results: The hormone receptor positivity threshold was 1% for 66% of
physicians. 28 % of them define the secondary hormone resistance as
recommended by the ABC consensus. The definition of visceral crisis is
not clear for 88.5%. 52% define it as the association of visceral metastases
+ clinical signs. 28% as visceral metastases + biological abnormalities.
Percentage of patients who are put on hormone therapy as a first
line therapy are 10% for 58% of oncologist and 50% for 27%. A second
line endocrine therapy is done by 78% of physicians. The presence of
visceral metastases (independently of visceral crisis) has an impact on
the physician’s decisions on 73% of cases. After chemotherapy, 69% of
oncologists prescribe maintenance endocrine therapy. ABC consensus is
the second recommendation used by Moroccans oncologist.
EPIDEMIOLOGY AND THERAPEUTIC MANAGEMENT OF METASTATIC
BREAST CANCER IN BULGARIA: A RETROSPECTIVE COHORT STUDY
PR84
Konstanta Timcheva2, Margarita Taushanova2, Krassimir Koynov1
1Multiprofile Hospital for Active Treatment “Serdika”, Medical Oncology,
Sofia, Bulgaria; 2Women’s Health Hospital “Nadezhda”, Medical Oncology
Clinic, Sofia, Bulgaria
Background: There are no established standards of care as well as scarce
insightful real life data about the current management of metastatic
breast cancer (MBC).
Objectives: The primary objective of this multi-center, retrospective,
non-interventional study was to estimate the incidence rate of disease
progression in a cohort of patients newly diagnosed with MBC, either
de novo or having progressed from a non-metastatic stage. Clinical
management and progression free survival (PFS) rates at 12 and 18
months after diagnosis of MBC were key secondary objectives.
Methods: Disease progression incidence rate was expressed as the
number of progression events (documented progression or death due to
any cause after diagnosis of MBC) on a per patient-year-basis. PFS rates
at 12 and 18 months were calculated with the Kaplan-Meier method.
Descriptive analysis was used for clinical management patterns after
MBC diagnosis.
Results: 171 patients were enrolled. The incidence rate of disease
progression per patient-year in 158 patients with full data was 0.477
[95% confidence interval (0.387, 0.582)]. The estimated probability of
PFS was 0.6114 [95% confidence interval (0.5279, 0.6847)] at 12 month
and 0.4558 [95% confidence interval (0.3732, 0.5346)] at 18 month after
diagnosis of MBC. The mean duration of chemotherapy for all enrolled
FULVESTRANT COMBINED WITH CAPECITABINE MAY BE
EFFECTIVE AND WELL TOLERATED FOR PATIENTS WITH ESTROGEN
RECEPTOR-POSITIVE, HER2-NEGATIVE METASTATIC BREAST CANCER
Maki Nakai
Nippon Medical School Hospital, Breast Oncology Dpt., Bunkyouku, Japan
Endocrine therapy concomitant use of chemotherapy remains to be
standardized in breast cancer patients; in a phase II study, however, an
efficacy and low toxicity of safulvestrant combined with capecitabine
was shown in estrogen receptor (ER)-positive, HER2-negative metastatic
breast cancer (MBC). In 2013, we began to treat patients with ER-positive,
HER2-negative MBC in our clinical practice, with high dose (500 mg)
fulvestrant combined with capecitabine as one of treatment options. In
this study we retrospectively analyzed the efficacy and toxicity of this
treatment in MBC patients. A consecutive series of 5 patients with ERpositive, HER2-negative MBC treated with fulvestrant combined with
capecitabine simultaneously were analyzed. Median age at an initial
diagnosis of MBC was 61 years (range, 50 to 68 years). Performance
status (PS) 0 was observed in 3 patients and PS 1 in 2 patients. MBC
was diagnosed at 49, 80, 92, and 119 months after surgery in 4 patients
and it was diagnosed at presentation (stage IV) in 1 patient. MBC was
diagnosed at 49, 80, 92, and 119 months after surgery in 4 patients and it
was diagnosed at presentation (stage IV) in 1 patient. Patients received
500 mg fulvestrant on days 1, 15, and 29, and then every 28 days
thereafter. Patients simultaneously received capecitabine, 1800 mg or
Abstracts / The Breast 24 S3 (2015) S21–S75
2400 mg per day on days 1 to 21 every 28 days. Fulvestrant combined
with capecitabine was administered as 2nd, 3rd, or 4th regimen of MBC
following progression of fulvestrant monotherapy in 3 patients, and
it was administered as 2nd or 4th regimen following progression of
other regimens without fulvestrant in 2 patients. Fulvestrant combined
with capecitabine was administered as 2nd, 3rd, or 4th regimen of
MBC following progression of fulvestrant monotherapy in 3 patients,
and administered as 2nd or 4th regimen following progression of
other regimens without fulvestrant in 2 patients. Chemotherapy was
an initial treatment in 1 patient with stage IV disease. Best responses
were as follows. Partial response (PR) and stable disease (SD) were
observed in 3 and 2 patients, respectively. Time to progression (TTP)
was 15 months in 1 patient; however, 4 were censored in TTP analysis
(3, 4, 7, and 13 months). No grade 3 or 4 adverse events were observed
in fulvestrant combined with capecitabine regimen. Grade 2 palmarplantar erythrodysesthesia was observed in 2 patients, in one of whom
the dose of capecitabine was reduced. No other grade 2 adverse events
were observed. Our retrospective study indicates that fulvestrant
combined with capecitabine is effective and well tolerated for patients
with ER-positive, HER2-negative MBC. Further analyses will be needed
in a prospective study setting.
PR85
OUR TREATMENT STRATEGY FOR PATIENTS WITH
HORMONE-RECEPTOR-POSITIVE, HER2-POSITIVE METASTATIC
BREAST CANCER
Haruo Tanaka1, Shuyo Umeda1, Souichiro Murakami1,
Mikimasa Ishikawa1, Kimiharu Tanaka2, Akihiko Uchiyama1
1
JCHO Kyushu Hospital, Surgery, Kitakyushu, Fukuoka, Japan;
2
Saiwaimaigeka Clinic, Surgery, Kitakyushu, Fukuoka, Japan
Goals: TAndem Study and eLEcTRA trial showed that the combination
of aromatase inhibitors (AIs) and trastuzumab is a safe and effective
treatment option for patients with epidermal growth factor receptor
2 (HER2) and hormone receptor (HR) positive metastatic breast cancer
(MBC). Our goal is to re-validate these evidence, such as the safeness
and efficacy of trastuzumab and AIs combination therapy for Her2 and
HR positive MBC patients.
Methods: We experienced 7 patients with HER2 and HR positive
postmenopausal MBC patients. Four patients were treated with
trastuzumab and AIs, and three patients were treated with trastuzumab
and chemotherapy. No patients were treated without trastuzumab.
Our indication of the combination therapy (trastuzumab and AIs) is
restricted only non-life threatening MBC.
Results: Patients treated with trastuzumab and AIs, three patients had
clinical benefit. Only one patient with liver metastasis had no response
and moved into chemotherapy plus trastuzumab. Especially, two
patients with only lymph nodes metastasis showed complete response
(one pathlogical complete response and one clinical complete response
for three years) with trastuzumab and AIs. Adverse events including
congestive heart failure are not observed in these patients.
Conclusion: The combination therapy of AI and trastuzumab is a safe
and effective treatment for patients with HER2 positive and HR positive
MBC. Especially for non-life threatening metastatic site (lymph node,
bone), this therapy is more sustainable for long periods without severe
side effect than trastuzumab plus chemotherapy.
S51
PR86
RETROSPECTIVE STUDY OF EVEROLIMUS WITH FULVESTRANT IN
POSTMENOPAUSAL WOMEN WITH HORMONE RECEPTOR-POSITIVE
METASTATIC BREAST CANCER PRETREATED WITH AROMATASE
INHIBITORS(AI’S) AND SELECTIVE ESTROGEN MODIFIERS
Leen Vanacker
Universitair Ziekenhuis Brussel, Medical Oncology Dpt., Brussels, Belgium
We conducted a retrospective analysis of postmenopausal women with
hormone receptor-positive metastatic breast cancer pretreated with AI’s
and fulvestrant. We aimed to look at the response rate, clinical benefit rate
and safety profile. The patients were administered monthly fulvestrant
500 mg I.M. and oral everolimus 7.5 mg daily. Results: Eight women with
hormone receptor positive HER2 negative metastatic breast cancer were
retrospectively included. The median age was 54.5 years old (range 4770). All tumors were ER-positive and the majority was PR-positive (75%).
Three patients (37.5%) were diagnosed with de novo metastatic disease.
The most common sites of metastases were bone and liver with 75% of
patients having three or more sites of metastatic disease. All patients
were heavily pretreated with endocrine therapy and received previously a
SERM, AI and fulvestrant. Five patients (62.5%) had a partial response and
2 patients (25%) had stable disease with a clinical benefit rate of 57.1%.
One patient was not evaluable for response due to rapidly progressive
disease. The median time to progression was 30 weeks and the median
overall survival was 22.5 months. All patients experienced some toxicity.
The most common adverse events were edema (75%), mucositis (50%),
diarrhea (50%), cough (50%) and metabolic changes (hyperglycemia
(87.5%), hypertriglyceridemia (65.2%), and hypercholesterolemia (50%).
Most common side effects were grade 1 or 2 and reversible with infrequent
need for everolimus dose reduction. Four patients (50%) required dose
reduction of everolimus due to edema, liver toxicity or infection. On the
reduced dose there was an amelioration of the side effects. Most reasons
for discontinuation were disease progression (71.5%) and drug related
toxicity (28.6%). In conclusion, our findings suggest that the combination
of everolimus with fulvestrant in postmenopausal women with hormone
receptor-positive metastatic disease, who progressed on prior AI’s and
fulvestrant, is an efficacious treatment option with an acceptable toxicity
profile. Further randomized studies are needed to confirm these findings.
PR87
COMBINATION THERAPY PERUZUMAB, TRASTUZUMAB AND
DOCETAXEL FOR ADVANCED OR RECURRENT BREAST CANCER
PATIENTS IN THE LATE LINE
Takashi Morimoto, Shintaro Michishita
Yao Municipal Hospital, Breast Surgery Dept., Yao, Osaka, Japan
Purpose: Combination therapy pertuzumab(PER), trastuzumab(HER)
and docetaxel (DTX) is the standard regimen for advanced or recurrent
breast cancer patients in the first line. The purpose of this study is
to evaluate the effect of this combination therapy as the late line for
advanced or recurrent breast cancer patients.
Patients and Methods: Seven patients were evaluated (age 47-70).
Three cases were administered as third line and others were as four or
more lines. Six cases had pulmonary and/or liver metastasis and one
had the distant LN metastasis. Five cases were HER2 type and two were
luminal HER2 type.
Results: The mean duration of administrated is 5.9 months (2-13 mo.
Median 4 mo.). Three cases are still administrating and two of them
were maintaining by PER and HER. Response rate is 43% (3PR, 1NC,
1PD and 2NE). The most of side effects were caused by DTX (alopecia,
neuropathy and dysgeusia). All patients are alive at that time.
Discussion: This regimen showed relative high response rate and long
term administration as the third or more line. This combination therapy
may be useful for HER2 positive advanced or recurrent breast cancer
patients as the late line.
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Abstracts / The Breast 24 S3 (2015) S21–S75
PR88
EXPERIENCE WITH ERIBULIN IN THE TREATMENT OF METASTATIC
BREAST CANCER IN TATARSTAN REPUBLIC CLINICAL ONCOLOGICAL
DISPENSARY
Alfyia Khasanova1, Guzel Mukhametshina1, Sufyia Safina2
1
Tatarstan Republic Clinical Oncological Dispensary, Chemotherapy dpt
#1, Kazan, Russian Federation; 2Tatarstan Republic Clinical Oncological
Dispensary, Chemotherapy dpt #3, Kazan, Russian Federation
Background: Disseminated breast cancer is chronic systemic disease
that requires long-term personalized drug therapy with rapidly
alternating regimens. Eribulin routinely practiced in Russia since 2013
can increase the life expectancy of such patients, effectively blocked
tumor growth.
Material and Methods: 7 patients received eribulin from March 2014 to
March 2015. The average age was 53 years old. All patients had already
got from 1 to 3 lines of chemotherapy due to metastatic disease. Three
patients received eribulin as second-line therapy, another three - in
the third line therapy, one patient - in the fourth line of therapy. Three
patients had hormone-positive breast cancer, 3 patients were HER2
neu positive, 4 patients had HER2-negative tumors (two of them were
triple-negative). All patients previously received anthracyclines and
taxanes. Patients received eribulin in monotherapy, 6 patients received
a dose of eribulin mezylate 1.4 mg/m 2, and 1 patient initially received
a reduced dose of the drug in 1.1 mg/m2 due to increased liver enzymes
after previous treatment. Eribulin was administered in the 1st and 8th
days of a 21 day cycle IV bolus. Evaluation of the effect was based on
physical examination and CT scan every 6-8 weeks. All patients were
treated until disease progression.
Results: Six patients have visceral metastases, one patient had local
recurrence in the area of operation and remote lymph nodes. Liver
lesions were in 4 patients, lung lesions - in three patients, in three
patients there were bone metastases. Most patients had multiple
combined lesions, only 1 patient had isolated lung metastases. One
patient had combined lung, liver and brain metastases. All patients
received 3 to 14 cycles of eribulin, the median duration of therapy
was 16 weeks. Survival to progression ranged from 3 to 10 months,
the median progression-free survival was 5.5 months. This 10-month
disease-free period was observed in patients who received eribulin as
chemotherapy 4th line (thus the maximal duration of effect of other
chemotherapy drugs in earlier lines of treatment should not exceed
6 months). In 2 patients, including patient with brain metastases,
achieved stable disease, treatment is ongoing. Most common adverse
events were hematological and hepatological: leukopenia, neutropenia,
increased ALT, AST, headache. Maximal toxicity was grade 2 (according
to the criteria STCAE 4.0). No serious adverse effects during treatment
with eribulin were observed.
Conclusions: Eribulin provides a significant effect in patients with
metastatic breast cancer when used in the 2nd and the following lines
of chemotherapy. Side effects of therapy usually do not lead to drug
discontinuation and easily stopped, without compromising the quality
of life of patients.
PR89
INFLAMMATORY BREAST CANCER – DOES DERMAL LYMPHATIC
INVASION INFLUENCE THE OUTCOME?
Daniela Kolarevic, Zorica Tomasevic
Institute for Oncology and Radiology of Serbia (IORS), Daily Hospital for
Chemotherapy, Belgrade, Serbia
Background: Inflammatory breast cancer (IBC) is one of the most
aggressive forms of locally advanced breast cancer (LABC). Its typical
clinical presentation is an inflammation of the breast skin, not due to
true physiological inflammatory response but rather as a consequence
of the dermal lymph vessels of the breast being blocked by cancer cells
forming tumour emboli. Even with an adequate number of tissue-block
samples and multiple sections (≥10), dermal lymphatic invasion (DLI)
is evident in up to 80 % of patients with true primary IBC. However,
the diagnosis of IBC is still made primarily on clinical grounds because
the absence of DLI does not exclude the diagnosis. The aim of this
retrospective analysis is to evaluate whether the presence of dermal
lymphatic invasion influences the response to induction chemotherapy
(iCT), time to progression (TTP) and overall survival (OS).
Methods: We evaluated 63 medical records of patients with IBC, stage
III, registered at the Institute for Oncology and Radiology of Serbia, in a
period between January 2008 and December 2010.
Results: Thirty two patients (51%) had a pathological confirmation of
DLI by multiple-site skin biopsy. No significant difference has been
observed between DLI positive (DLI+) and DLI negative (DLI-) groups
in terms of age, menopausal status, BMI, pathohistological tumour
type or tumour size. Evaluation after 4 cycles of anthracycline-based
iCT showed that partial response (PR) or stable disease (SD) have been
achieved in only 59% patients with DLI, compared to 93% of DLI negative
patients (including one patient with confirmed complete response).
Disease progression (PD) during iCT was observed in 41% and 6% of
DLI+ and DLI- patients, respectively. After the good initial response to
iCT and disease stabilisation, during the median follow up period of
36 months (ranges 12-42 months), the relapse has been detected in 9
out of 19 DLI+ patients (47%; median TTP was 28 months) and 10 out of
29 DLI- patients (34%; median TTP was 32 months). Nineteen patients in
a DLI positive group died (60%; OS was 20.7 months), compared to nine
patients in DLI negative group (29%; OS was 25.5 months).
Conclusion: Our study suggests that patients who do have dermal
lymphatic invasion confirmed alongside with the IBC diagnosis are more
likely to have poorer response to induction chemotherapy, as well as
shorter TTP and shorter OS. Therefore, it could be expected that proven
skin involvement is responsible for the high metastatic potential and it
might represent a very important factor for generally poorer prognosis
of patients with IBC.
PR90
BASIC CLINICAL ISSUES OF INFLAMMATORY CARCINOMA OF THE
BREAST
Arjeta Bebeci-Docaj
Hygeia Hospital, Radiology Dpt., Tirana, Albania
Is a uncommon breast carcinoma but aggressive form which has a
characteristic clinical presentation and unique radiographic appearance.
Inflammatory carcinoma account for 1-4% of all breast cancer typically
occurring in women between 4th to 5th decade. Clinically inflammatory
breast cancer mimics mastitis. The breast is enlarged often relatively
short onset, indurate, erythematous, warm tender and painful. The
skin is thickened and edematous with a peau d’orange appearance.
There may or may not be an underlying palpable mass. The breast
is not painful in spite of the alarming appearance on examination.
The condition may also present with flattening, erythema, crusting,
blistering or retraction of the nipple. Fixed palpable ipsilateral axillaries
lymph nodes synonymous with metastatic disease are frequently
observed. However systemic symptoms such as fever are absent which
helps somewhat differentiate from mastitis. Rapid progression of the
disease with associated erythematic affecting more than one third of
the skin often distinguishes true IBC from a neglected locally advanced
breast cancer that has developed inflammatory changes. IBC has a
tendency to metastasize at an early stage. In cases where a biopsy does
not give the diagnosis, skin biopsy may be indicated. Unlike other types
of breast carcinoma in which surgery is the first modality of treatment,
chemotherapy before surgery or radiation therapy is the current
standard therapy.
[1] Carlson RW, Allred DC, Anderson BO, Burstein HJ, Carter WB, Edge
SB, et al. Breast cancer. Clinical practice guidelines in oncology. J
Natl Compr Canc . 2009;7:122-92.
[2] Chlebowski RT, Kuller LH, Prentice RL, Stefanick ML, Manson JE,
Gass M, et al. Breast cancer after use of estrogen plus progestin in
postmenopausal women. N Engl J Med. 2009;360:573-87.
Abstracts / The Breast 24 S3 (2015) S21–S75
[3] Hayes DF. Clinical practice. Follow-up of patients with early breast
cancer. N Engl J Med. 2007;356: 2505-13.
[4] Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breastcancer prevention in postmenopausal women. N Engl J Med.
2011;364:2381-91.
PR91
NO PALLIATIVE SYSTEMIC ANTINEOPLASTIC THERAPY IN PATIENTS
WITH DISTANT METASTATIC BREAST CANCER: A BLIND SPOT IN THE
PERCEPTION OF ONCOLOGY?
Uwe Güth2,3, Dorothy Huang5, Seraina Schmid4,1
1
Breast Center St. Gallen, Spital Grabs, Grabs, Switzerland; 2Cantonal
Hospital Winterthur, Obstetrics & Gynecology, Winterthur, Switzerland;
3
Cantonal Hospital Winterthur, Breast Center “Senosuisse”, Winterthur,
Switzerland; 4Spital Grabs, Gynecology & Obstetrics, Grabs, Switzerland;
5
University Hospital Basel, Gynecology & Obstetrics, Basel, Switzerland
Introduction: Oncologists learn from their daily experiences with their
patients. Following the progression and course of their diseases, which
may last for years, increases their knowledge and clinical competence.
In this study, we focus on a special situation of metastatic breast cancer
(MBC) which is often overlooked by many oncologists. Patients who die
from MBC without receiving palliative systemic antineoplastic therapy
comprise a potential “blind spot” in the field of oncology.
Methods: From all patients who were recorded in the Basel Breast
Cancer Database with MBC (diagnosis of MBC: 1990-2011, n=369), we
had complete information regarding the course of palliative therapy and
outcome in 363 cases (98.4%). Of those, we evaluated the 323 patients
(89.0%) who ultimately died of their metastatic disease.
Results: The general type of palliative treatment was as follows:
endocrine therapy only, n=68 (21.1%); chemotherapy only, n=86 (26.6%);
combination regimen including endocrine therapy and chemotherapy,
n=128 (39.6%). Forty-one patients (12.7%) did not receive systemic
antineoplastic therapy in the palliative situation. The distribution
dependent on age at first diagnosis of MBC was as follows: ≤59 years:
10/125 patients (8.0%); 60-69 years: 10/85 patients (11.8%); ≥70 years:
21/113 patients (18.6%).
Compared to patients who had received palliative antineoplastic
systemic therapy, those who remained untreated were significantly
older (71 vs. 63 years, p<0.001), had shorter metastatic disease survival
(2 vs. 24 months, p<0.001) and had more often secondary MBC (95.1%
vs. 73.8%, p=0.002); furthermore, they had more often already declined
systemic therapy in the adjuvant situation (12.8% vs. 4.8%, p=0.068).
Discussion: Not surprisingly, a lack of treatment was most commonly
seen in the subgroup of patients ≥70 years, since the physical condition
and frequent comorbidities of these patients make oncologic therapies
often impossible. However, in the subgroup of younger patients,
approximately 10% also had not received any therapy before breast
cancer-related death occurred. This group of younger women rarely
had any relevant comorbidities and were potential candidates for
chemotherapy. Most patients in this group were individuals who
knowingly declined therapy. Despite the undisputed successes of
modern therapy approaches, a certain percentage of the population may
have a profound mistrust of and aversion to modern western medicine
and decline such treatment. Skepticism of more aggressive therapy
regimens is also reflected in the fact that in the group of patients who
died of MBC and received treatment, approximately 25% only had
endocrine regimens, and of these patients, around 20% were younger
than 60 years. Patients who do not receive antineoplastic therapy in the
palliative situation of MBC are rarely ever even seen by a specialized
oncologist and thus play little role in their perception of the disease;
nevertheless, these cases comprise an important part of the entity
“metastatic breast cancer”.
S53
PR92
NATIONAL CLINICAL BREAST CANCER REGISTRY: VIEWS AND
APPROACHES
S. Pramod
Health Alert Organisation of India, Health Dpt., Garud colony, Deopur,
Dhule, India
Background: Cancer registry provides for health professionals/
researchers detailed information on incidence, trend and survival
statistics. Cancer registries are population-based and seek to describe
incidence, rates and trends of breast cancer within set populations. Also
provide info on staging, treatment and allied clinical data required to
monitor clinical care/outcomes. Development of such comprehensive
database on breast cancer is long awaited in India.
Objective: Our cancer NGO developed primary plan in consultation
with four divisional hospitals and Health ministry. We aim to establish
platform for multi-clinician, multi-centric collation of oncology datasets
with breast cancer as pilot disease entity. We plan to integrate this
concept at major cancer institutes with expertise from ESO. Proposal of
intent has been approved at national level.
Methods: Here we relate our experience of an initiative aimed at
establishing methodology, statistical analysis and supportive control
center for multicollaborator breast cancer data collection, aiming to
establish national breast cancer data repository.
Results: Initiated from four sites, modern technology of data
collection, storage and analysis and distribution is optimized towards
implementation of sustained comprehensive and multi-collaborator
data registry. Need for minimum datasets, customization of technology
to suit needs, data capture, storage and retrieval. These can be leveraged
to inform future direction of initiatives: expanding scope of database,
optimizing variables for data analysis and addressing data privacy,
security and ownership concerns. We have developed our model
database but need participation of private cancer care institutes and
naturopathy clinics. Total participants projected by 2013 are 46.
Conclusion: Our experience with this initiative over past three years
has shown that data can be collated centrally in secure/private manner.
Multicentre, multi-clinician collaboration is possible with collaborative
efforts with ESO/WHO. Major concern is haphazard data/protocol
maintenance by private entities. Most difficult data outsourcing was
about survival statistics. National breast cancer Registry is distant dream
in resource-poor-nations. But we have taken step in forward direction
on this burning issue.
PR93
THE CHANGES OF PLATELET-LYMPHOCYTE RATIO AS A SENSITIVE
TUMOR MARKER TO PREDICT PROGRESSION IN METASTATIC BREAST
CANCER
Masahiro Kashiwaba, Hideaki Komatsu, Kazushige Ishida,
Yusuke Matsui, Ryoko Kawagishi, Hanae Otsuki
Iwate Medical University, Surgery, Morioka, Japan
Recent studies reveal the clinical impacts of immunological background
between breast cancer and host, i.e. tumor infiltrating lymphocyte and
higher platelet-lymphocyte ratio (PLR) which may represent cachexia or
worse condition related to poor prognosis. Although these phenomena
were reported about primary tumors, biomarkers expressing
aggressiveness of metastatic breast cancer (MBC) should be clinically
more important. In order to evaluate clinical impacts of PLR in MBC, pts
treated by chomo/anti-HER2- or endocrine therapies were investigated
whether representative tumor markers (TMs), CEA and CA15-3 and PLR
can predict the progression of disease with confirmation by CT/bone
scans.
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Abstracts / The Breast 24 S3 (2015) S21–S75
PR94
TUMOR MARKER (CA 15-3) MONITORING FAILED TO DETECT DISEASE
RELAPSE AND TRIGGERED UNNECESSARY PROCEDURES – REPORT OF
TWO CASES
Ivan Bilic
University Hospital Center Zagreb, Medical Oncology, Zagreb, Croatia
Introduction: Despite robust study data along with consensual
guidelines corroborating futility of tumor marker measurement as
screening criterion for metastatic spread after breast cancer (BC)
treatment, this practice is still not uncommon among oncologists. Tumor
markers are neither sensitive nor specific enough for early relapse/
dissemination detection, with consecutive rise-up of healthcare costs.
This case report describes false-positive and false-negative findings
in two cases, in an attempt to illustrate need for discouragement of
further use of tumor markers as clinical tools for relapse detection, thus
pointing to possible money-saving change of practice.
Case report 1: 65 yr. old patient is referred to PET-CT after mild but
constant rise of tumor marker 7 months after surgery for BC. No signs of
relapse were confirmed but thyroiditis is suspected. Following thyroiddisease confirmation and treatment commencement CA 15-3 level
decreased. After three months relapse of breast cancer was confirmed
by mammography and ultrasound-guided biopsy, with bone metastatic
spread confirmed by scintigraphy.
Case report 2: 68 yr. old patient experiences slight rise of tumor
marker 15 years after primary BC treatment. After serious suspicion
for metastatic spread to mediastinal lymph nodes is raised by PET-CT,
she undergoes surgical lymphadenectomy with no evidence of tumor
tissue. Three years of further follow-up revealed no other suspicion of
metastatic disease, despite moderate elevation of serum tumor marker.
Recorded rise of CA 15-3 could retrogradely be attributed to liver
steatosis seen on abdominal ultrasound.
Discussion: Breast cancer designated tumor markers (CEA, CA 153, CA 27.29) could be routinely used at oncologist’s discretion in the
metastatic setting of BC according to recent guidelines. On the other
hand, prescription of marker-testing after primary BC treatment could
still be recorded at surprisingly high level, thus leading to unnecessary
costs and clinical consequences. In the context of unmet healthcare
needs for costly treatments of advanced breast cancer patients in many
countries, practice of upfront tumor marker measurement should be
considered as preventable resource-dissipation and avoided outside the
setting of confirmed metastatic progression.
PR95
PARANEOPLASTIC CEREBELLAR DEGENERATION AND BREAST CANCER
Diana Freitas, Ana Marques, Joana Cunha, Catarina Portela, Rui Nabiço
Hospital de Braga, Medical Oncology Dept., Braga, Portugal
Introduction: Paraneoplastic neurological syndromes are neurologic
manifestation associated with onconeural antibodies without the
presence of brain metastases. It’s a rare diagnostic that appears in less
than 1% of the patients with malignancies, being well known in small
cells carcinoma of the lung and less in breast cancer.
Clinical case: Female patient, 46 years old, with a past health history
irrelevant. In August 2013, she was admitted in Emergency Room with
progressive difficulty of gait and diplopia with 1 month of evolution,
with the need of a wheelchair. In physical exam with oscillopsia,
dysmetria and ataxic gait. Breast exam normal. In right axilla, a palpable
adenopathy with 2 cm, hard, painless and deep layers. Gynecological
examination without alterations. Magnetic resonance (MR) of the spine
and brain revealed a hypersign in the right posterior parietal subcortex.
Cerebrospinal fluid was normal with virus, borrelia and microbiologic
exam negative. Thorax, abdomen and pelvic CT scan showed several
adenopathies in the right axilla. Endometrial cavity with accented
hypodensity and increase of the dimensions of the uterine cervix.
Cervical-vaginal cytology was considered normal. Hysteroscopy and
biopsies of endometrium normal. Mammography normal and breast
ultrasonografy demonstrated on right axillary lymph nodes with
1.9×1.2cm. Biopsy of axillary nodes revealed metastasis of breast
carcinoma, with estrogen receptors and Her2 positive. Breast MR without
suspicion image. Laboratory finding with ANA positive (1/80) and anti Ri
positive (3 +), Anti HU, anti Yo, CV2 Amphisysin, PNMA negative. Initiated
treatment with immunoglobins (5 days) without significant clinical
improvement. In multidisciplinary team consultation was decided
to start treatment with chemotherapy with sequential scheme of
anthracycline and taxane associated to trastuzumab (TZ). After 8 cycles
with disappearance of the nystagmus and ataxic gait having recovered
the total autonomy. Imagiologic evaluation without evidence of axillary
disease. She underwent a modified radical mastectomy in March 2014.
Anatomopathological analysis showed no residual neoplasm and
absence of metastases in 21 lymph nodes isolated of the right _ ypT0 N0
CR. The patient received adjuvant radiotherapy and completed 1 year of
TZ. Began hormone therapy with tamoxifen that still doing. In the last
evaluation (March 2015) the patient still asymptomatic.
Conclusion: The authors report this case to alert for the rarity of this
syndrome and the need of fast detection and immediate treatment
of the tumor to give to the patient the best chance of stabilizing and
preventing further neurological deterioration.
Clinical Issues: Radiation Oncology
P096
CHARACTERISATION OF BREAST CANCER BRAIN METASTASES
THROUGH A 21-YEAR PERIOD – A STUDY FROM THE SWEDISH
ASSOCIATION OF BREAST ONCOLOGISTS (SABO)
Anna Thulin3, Elisabeth Werner-Rönnerman3,6, Mattias Sundén1,
Shahin de Lara6, Arnd Schoenfeldt5, Michael Wallberg2,
Chaido Chamalidou3,7, Anikó Kovács3,6, Fredrik Enlund6,
Barbro Linderholm3,4
1
Gothenburg University, Department of Economics, Gothenburg, Sweden;
2
Halland Hospital at Varberg, Department of Surgery, Halmstad, Sweden;
3
Institution of Clinical Sciences, Department of Oncology, Gothenburg,
Sweden; 4Karolinska University Hospital, Department of OncologyPathology, Stockholm, Sweden; 5Norra Älvsborg County Hospital,
Department of Pathology, TROLLHÄTTAN, Sweden; 6Sahlgrenska University
Hospital, Department of Pathology, Gothenburg, Sweden; 7Södra Älvsborgs
Hospital, Department of Oncology and Hematology, Borås, Sweden
Background: Median survival after diagnosis of breast cancer brain
metastases (BCBM) is only 3 to 12 months. Existing theories claim that
BCBM is an increasing clinical problem likely due to adjuvant therapies
not passing the blood brain barrier (BBB).
Aims: To attempt to describe 197 patients with BCBM diagnosed in the
west of Sweden between 1994 and 2014 with regards to receptor status,
time from primary BC to diagnosis of BCBM, survival compared to extent
of BCBM and to BC subgroup.
Method: Records from patients with BCBM diagnosed 1994-2014 were
studied. Clinical data and expression of oestrogen (ER), progesterone
receptor (PgR) and human epidermal growth factor receptor 2 (HER2)
was extracted. Difference in time from primary BC to comfirmed BCBM
were compared between 1994-2004; 2005-14 with Mann-Whitney test.
Survival according to extent of BCBM and expression of the ER, PgR and
HER2 calculated by Kaplan-Meier and log-rank.
Results: Data was studied for 197 patients. Fifty patients (25%) displayed
brain metastases solely and 104 (53%) had other metastases prior to
BCBM; 43 (22%) were diagnosed with other metastases after or at the
time of BCBM diagnosis. A total of 116 patients (59%) had BCBM in the
cerebrum, 25 (13%) in the cerebellum and 43 (22%), in both cerebrum
and cerebellum concurrently. Seven patients (4%) displayed meningeal
carcinomatosis (MC) solely. Twenty-one patients (11%) had both. Seventysix patients (38%) underwent surgery with in all cases but seven also
radiotherapy (RT), 10 patients (5%) received stereotactic radiotherapy,
83 patients (42%) received whole brain irradiation whilst 28 patients
Abstracts / The Breast 24 S3 (2015) S21–S75
(14%) received no treatment. Data on ER, PgR and HER2 was available
in 172 (87%), 161 (82%) and 127 (66%) patients respectively. Expressions
of the receptors were: HER2 positive (22%), HER2 negative (42%) and
unknown (34 %); ER positive (49%), ER negative (38%) and unknown
(12%); PgR positive (31%), PgR negative (50%), unknown (18%). Forty-one
patients (21%) were confirmed triple negative. Our preliminary results
show a significant difference in survival according to disease extent (1-2
BCBM vs ≥3 BCBM vs MC) (p=0.0004) (n=195). Differences were found in
pairwise comparisons between 1-2 vs ≥3 BCBM (p=0.0013) and between
1-2 BCBM and MC (p=0.0059) whilst none was seen between ≥3 BCBM
and MC (p=0.0812). Survival was influenced by BC subgroup (p= 0.0278)
(n=127); worst outcome for patients with for TNBC but no difference in
a comparison between luminal and HER2 positive BC. Time to diagnosis
of BCBM was equal throughout the period (p=0.84). Data divided into
intrinsic BC subgroup in the whole patient cohort after review by two
independent pathologists and differences in biomarker expression
between primary tumour and BCBM will be presented.
PO97
BRAIN METASTASES IN HER2- POSITIVE BREAST CANCER PATIENTS:
A SINGLE INSTITUTE EXPERIENCE
Tahir Mehmood3, Asma Rashid3, Muhammad Irfan3, Sumera Nighat2,
Bilal Aziz1, Mazhar Ali Shah3
1
Lahore General Hospital, Radiology, Lahore, Pakistan; 2Nishter Hospital
Multan, Radiology, Multan, Pakistan; 3Shaukat Khanum Memorial Cancer
Hospital and Research Centre, Radiation Oncology, Lahore, Pakistan
Background: Human epidermal growth factor receptor 2- positive
breast cancer (HER2+ BC) accounts for approximately 20% of all cases
of breast cancer and have an aggressive course in metastatic setting due
to distinct natural history. Brain metastasis is diagnosed in up to 40% of
patients with HER2+ BC and is associated with substantial morbidity and
mortality. In the present study, we aimed to investigate the incidence of
brain metastases in patients with HER2+ BC treated at our institute.
Materials and Methods: Between 1995 to 2009, the hospital information
system identified 513 women with pathologically confirmed HER2+
breast cancer. Median age was 45 years (range 20-75 years). AJCC stage;
stage I 7%, stage II 58% and stage III 35% of the patients respectively.
Histological sub-types; infiltrating ductal carcinoma 96%, infiltrating
lobular carcinoma 2% and others 2% respectively. Pathological grade;
grade I/II in 41% and grade III 59% of the patients. 70% of the patients were
treated with primary surgery. Chemotherapy regimens; adriamycin and
taxanes based 75%, adriamycin based 5%, CMF 9% and other regimens in
5% of the patients either in neo-adjuvant or adjuvant setting. Only 6%
of the patients received trastuzumab therapy. 5% of the patients did not
receive any type of chemotherapy or targeted therapy. Post-operative
radiotherapy was delivered to 86% of the patients. Incidence and median
time to brain metastases were determined.
Results: Median follow-up duration was 48 months. Patterns of failure;
local 5%, regional 2%, and distant metastases in 26% of the patients. 14%
of the patients who failed distantly were found to have brain metastases
as first site of relapse. Overall brain metastases were seen in 25% of the
patients. Median time to brain metastases was 13 months (range 8–50).
Conclusions: Our results suggest that HER2+ BC sub-type remains
more aggressive and is associated with a very high incidence of brain
metastases. Future studies should be focused on new therapeutic
options like small molecule tyrosine kinase inhibitors in adjuvant
setting to decrease the incidence of systemic relapse.
PO98
IS BRAIN METASTASES LOCATION ASSOCIATED WITH PROGNOSIS IN
BREAST CANCER PATIENTS?
Karolina Widera1, Dorota Gabryś2, Michał Jarząb3, Dawid Larysz2,4
1
Maria Skłodowska-Curie Memorial Cancer Center and Institute of
Oncology, Gliwice Branch, Outpatient Clinic, Gliwice, Poland; 2Maria
S55
Skłodowska-Curie Memorial Cancer Center and Institute of Oncology,
Gliwice Branch, Departmant of Radiotherapy , Gliwice, Poland; 3Maria
Skłodowska-Curie Memorial Cancer Center and Institute of Oncology,
Gliwce Branch, III Department of Radiotherapy and Chemotherapy,
Gliwice, Poland; 4Medical University of Silesia, Department of
Neurosurgery, Katowice, Poland
The paradigm of brain metastases (BM) treatment has recently shifted
towards the limited use of whole-brain irradiation and widespread
application of radiosurgery. The number of metastases and it’s
localisation, presence of extracranial disease, are potentially important
for surgical decision making, and less influential for the radiosurgical
treatment. There is suggestion that the location of metastases (supravs infratentorial +/-supratentorial) is not associated with the relapse
after radiosurgical treatment. The aim of this study was to analyze the
influence of brain tumor location on the prognosis in breast cancer
patients mainly treated by WBRT+/- radiosurgery.
Material and Methods: The group of patients was retrospectively
selected from the population of breast cancer patients treated due
to brain metastases by radiation therapy in MSC Memorial Cancer
Center and Institute of Oncology in Gliwice. By the analysis of
patient’s records we identified 315 pts treated between 2005-2014.
Patients’ median age at BM diagnosis was 56 years (range 28-83).
The majority (51.7%) presented good performance status (ECOG 0-1).
BM co-occuring with active disease outside the brain were diagnosed
in 218 pts (69.2%). Eighty seven pts (27,6%) presented with a single
metastatis, 68 pts (21,6%) with 2-3, and 160 pts (50,8%) with multiple
BM. Supratentorially located disease was found in 133 pts (42.2%), 37
pts (11,7%) have had infratentorial BM, while in 145 pts (46%) they
were located in both compartments. More detailed analysis of tumor
location (lobes, deep brain structures) was also carried out. All BM were
treated with radiotherapy, 89.8% underwent WBRT, 19.7% of patients
underwent additional metastasectomy, 39.7% stereotactic irradiation:
in combination with WBRT 29.5% or alone 10.2%. One hundred twenty
two pts (38.7%) underwent systemic treatment after BM diagnosis.
Statistical analysis was carried out by the use uni-and multivariate Cox
regression, with overall survival from the diagnosis of brain metastases
as the major endpoint in the study.
Results: Median OS from BM diagnosis was 6 months (0-119 months ).
The survival time was highly associated with the number of metastases
(p<0.05), and associated with the biological subtype of the tumor
(longest for luminal subtype, intermediate in HER2-positive disease,
shortest in triple negative disease, p<0.05). The presence of extracranial
disease and poor performance status were negatively impacting OS
(p<0.05). In the comparison of limited number of metastases (1-3)
located supratentorially, infratentorially and in both locations there
were no differences in the overall survival time (n.s.). The similar
pattern was observed in multiple metastases group (n.s.), although in
both strata the number of BM was stronger factor than their location.
Conclusion: Metastasis location in brain appears not to determine
prognosis in patients treated by radiation therapy.
PO99
TREATMENT OUTCOMES OF BREAST CANCER BRAIN METASTASES
Ivica Ratosa, Tanja Marinko, Andreja Gojkovic Horvat, Jasenka Gugic,
Manja Sesek, Mateja Bozic, Marija Snezna Paulin Kosir, Elga Majdic
Institute of Oncology Ljubljana, Department of Radiation Oncology,
Ljubljana, Slovenia
Background: Breast cancer (BC) brain metastases (BM) influence quality
of life and survival in metastatic BC. The purpose of this retrospective
study is to evaluate treatment outcomes in patients with BM, treated
with whole brain radiotherapy (WBRT) regarding to molecular subtypes,
clinical characteristics and available prognostic indexes (PI).
Methods: We retrospectively reviewed medical records of 133
metastatic BC patients treated with WBRT from April 2005 to December
2012 at Institute of Oncology Ljubljana. Intrinsic subtypes of BC were
defined as luminal A (ER+, HER2-, low Ki67, high PR+), luminal B HER2-
S56
Abstracts / The Breast 24 S3 (2015) S21–S75
negative (ER+, HER2-, high Ki67 or low PR+), luminal B HER2-positive
(ER+, HER2+, any PR/Ki67), HER2-enriched (HER2+, ER-) and triple
negative (ER-, PR-, HER2-). Prognostic groups of recursive partitioning
analysis (RPA), graded prognostic assessment (GPA), breast GPA and
simple survival score (including Karnofsky performance status (PS)
and extracranial metastases) for patients with BC BM (SS-BM) were
compared. Overall survival (OS) was calculated using the Kaplan-Meier
method. Cox regression model was used to evaluate prognostic values of
PI, clinical and biological characteristics.
Results: Median age at BC diagnosis, diagnosis of any metastatic disease
and BM diagnosis was 51.7, 56.6 and 58.6 years, respectively. At time of
BM diagnosis, 114 (85.7%) patients had extracranial disease. In addition
to WBRT, 27 (20.3%) patients had BM surgery. The median OS from BM
diagnosis was 8.3 months (CI 95%, 5.4-11.2). Asymptomatic patients at
time of WBRT had longest median OS of 21.0 months (CI 95% 9.2-32.7,
p<0.0005). WBRT improved BM symptoms in 85 (64%) patients, which
was significantly associated with improved median OS (12.3 versus 3.6
months, p<0.0005). 26 (19.5%) patients had luminal A, 18 (13.5%) luminal
B HER2-, 31 (23.3%) luminal B HER2+, 20 (15.0%) HER2-enriched and 18
(13.5%) triple negative tumors at BC diagnosis. Molecular characteristics
of 20 (15.0%) tumors were missing. Longest median OS of 13.5 (CI 95%,
8.2-18.7) and 13.0 (CI 95%, 2.2-23.9) months was seen in luminal B
HER2+ and HER2-enriched tumors, respectively. OS difference between
molecular subtypes was not statistically significant (p=0.070). In
multivariate analyses, better PS at time of WBRT (p<0.0005), BM surgery
(p=0.001), systemic hormonal therapy within 3 months before or after
WBRT (p=0.024), good prognostic groups of Breast GPA (p=0.003) and
SS-BM (p=0.027) were all significantly associated with OS improvement.
Conclusion: Patients with BM have different outcomes after WBRT,
regarding symptoms improvement and OS. Breast GPA and SS-BM
seem to be useful tools for personalised cancer treatment decisions in
palliative care for BC patients with BM.
PO100
IMRT-SIB FOR LOCALLY ADVANCED INOPERABLE BREAST CANCER
PATIENTS
Dorota Gabrys1, Roland Kulik1, Agnieszka Namysł-Kaletka1,
Iwona Wzietek1, Karolina Widera2, Krystyna Trela-Janus1
1
Maria Sklodowska-Curie Memorial Cancer Center and Institute of
Oncology, Radiotherapy, Gliwice, Poland; 2Maria Skłodowska-Curie
Memorial Cancer Center and Institute of Oncology, Gliwice Branch,
Outpatient Clinic, Gliwice, Poland
Radiobiological and clinical data suggest that higher dose per fraction
with shortening overall treatment time in breast cancer patients may
enhance locoregional control. This, ethics approved, prospective study
was designed to evaluate the technical feasibility, toxicity and early
results of simultaneous integrated boost (SIB) for locally advanced,
breast cancer patients. Eighteen women (8 right; 10 left sided) received
radiotherapy with SIB applying various dose levels in 30 fractions. Doses
were individualized according to the stage of the disease. The regional
lymph nodes received 49.8-60 Gy, df 1.66-2 Gy, metastatic lymph
nodes received 66-69.9 Gy, df 2.2-2.33 Gy, breast with chest wall was
irradiated with a dose 49,8-60 Gy, the whole breast to 60Gy, and the
highest dose was delivered to the breast tumour 69.9 Gy. Early toxicity
and results were prospectively recorded using CTCAE 4.03, QLQ 30, QLQ
Br23, and Lent Soma scale. All patients underwent planning CT or FDG
PET-CT. The majority (13 patients) were treated with the use of Clinac
IMRT-SIB, 5 patients were treated with Tomo-SIB. The median age was
59 years (range 37 – 78). Median tumor size was 6 cm (range 1-12 cm).
Almost all (13) patients presented with clinical stage IIIB of the disease,
one patient with IIIA, two with IIIC. Two patients in stage IIA were not
qualified to surgery, one was not suitable for resection due to medical
conditions, the second did not agree for a surgery. All patients received
chemotherapy, 11 patients FAC only, remaining various combinations
with taxanes. Ten patients were treated with hormonal therapy, the
majority of them (8 patients) were treated with tamoxifen. The mean
dose to the ipsilateral lung was 16 Gy (range 12.9 - 20.7). The percentage
of lung receiving >5Gy was 74.4, >10Gy - 50.3, >20Gy - 25.6. The mean
heart dose was 9.6 Gy (range 5.4 - 16.9) and V5Gy was 64.1, V10Gy 28.9, V30Gy - 4.9. There was significant decrease in WBC (median 6.2 vs.
4.9 × 103/ul; p-0.03), PLT (235 vs. 184 × 103/ul; p-0.01) before and after
radiotherapy. RBC and Hb did not significantly decrease. The maximum
Grade 3 early skin toxicity by the end of treatment was present only
in two patients. No Grade 4 toxicities were observed. The maximum
Grade 2 fatigue, Grade 1 dysphagia, Grade 1 pain with swallowing were
recorded. The early skin toxicity resolved in all patients evaluated one
month after finishing the treatment.
Conclusions: This 6-week course of definitive radiotherapy using SIB
technique showed to be feasible and was associated with acceptable
early skin toxicity. Long-term follow-up data are needed to assess late
toxicity and clinical outcomes.
PO101
PROGNOSTIC FACTORS AFTER GAMMA KNIFE RADIOSURGERY IN
BREAST CANCER PATIENTS WITH BRAIN METASTASES
Shoko Hayama3, Osamu Nagano2, Naohito Yamamoto1,
Takeshi Nagashima3, Rikiya Nakamura1, Masaaki Sakamoto4
1
Chiba Cancer Center, Division of Breast Surgery, Chiba City, Japan; 2Chiba
Cerebral and Cardiovascular Center, Gamma Knife House, Ichihara City,
Chiba, Japan; 3Chiba University, General Surgery Department, Chiba City,
Japan; 4Kameda Medical Center, Division of Breast Surgery, Kamogawa
City, Chiba, Japan
Backgrounds and Aim: Gamma knife radiosurgery (GK) is one of the
effective treatment options for brain metastases (BM) from breast
cancer. Some reports showed its efficacy on prolongation of survival.
However, the prognostic factors associated with good prognosis in BM
patients remains unclear. Therefore, we set out to clarify these factors.
Materials and Methods: We retrospectively analyzed the data of
70 breast cancer patients with BM who were treated with GK in our
institution from January 2005 to December 2014. We exploratory
examine the relationships between clinico-pathological factors and
overall survival (OS) after GK. Clinico-pathological factors included age
at initial diagnosis, performance status (PS), neurocognitive symptoms,
the number and volume of BM lesions, WBRT history, craniotomy
history, time to BM from the primary diagnosis, time to BM from the
first time of recurrence, the number of systemic therapies after GK, and
breast cancer subtypes.
Results: The median age at initial diagnosis was 48 (range 28-75). The
median KPS at diagnosis of BM was 90 (60-100). Fifty-two cases (74%)
had neurocognitive symptoms. The median number of BM was 3 lesions
(1-32). Twenty-four cases (34%) had a history of craniotomy and 18
cases (26%) had WBRT. The median period from primary diagnosis to BM
was 54 months (0-330) and the median period from the first recurrence
to BM was 14 months (0-171). The median number of systemic therapy
after GK was 1 regimen (0-7). In breast cancer subtypes, Estrogen
receptor (ER) positive/Human epidermal growth factor receptor 2
(HER2) negative, ER (+)/HER (+), ER(-)/HER2(+), ER(-)/HER2(-), were
21, 14, 17, 18 cases, respectively. The cases with PS2, neurocognitive
symptoms, WBRT history, or the number of GK1 had significant
relationships with poor OS after GK. The OS after GK in ER(+)/HER2(+)
group were significantly better than other subtypes (1-year survival rate
was 85%, p <0.05).
Conclusions: Our study showed that patients with no symptoms and
good PS at BM diagnosis demonstrated good prognosis after GK.
PR102
STERNAL RECURRENCE IN TREATED PATIENTS OF ADVANCED STAGE
CARCINOMA BREAST - AN EMERGING ENTITY
Divyesh Kumar
VCSGGMS&RI, Radiation Oncology, Srinagar, India
Abstracts / The Breast 24 S3 (2015) S21–S75
Background: Bone metastasis is a frequent complication of cancer.
It occurs in up to 70% of patients with advanced breast cancer. Breast
cancer has the tendency to relapse in the bones, and 56% of autopsy
cases reveal the occurrence of bone metastasis. The most frequent sites
of bone metastasis are the thoracic and lumbosacral spine. The present
analysis aims to bring forth an unusual site of bony recurrence in treated
patients of LABC (locally advanced carcinoma breast) and the effect of
palliative RT in these inoperable patients.
Material and Methods: 9 patients with sternum as site of metastasis
were detected during follow up of 10 months of post treated LABC
cases .All, except one, patient were on hormonal therapy at the time
of detection and had earlier undergone MRM, RT and chemotherapy
(CAF × 6 cyc). 6/9 patients were postmenopausal and 3/9 patients were
premenopausal. 6 patients had ER+,PR+ as receptor status, 2 patients
ER+,PR-ve and 1 patient ER-ve, PR-ve. Out of 6 receptor positive
(ER+,PR+ve) 4 patients were receiving tab. Letrozole while 2 were on tab.
tamoxifen. 2 patients with ER+,PR- were on tab. tamoxifen. Metastasis in
these patients was confirmed with bone scan (increased tracer uptake)
and FNAC from the sternal site (metastastic adenocarcinoma consistent
with breast primary), rest workup was negative for metastasis elsewhere.
All patients presented with swelling and pain at sternal site and were
found to be inoperable hence were given palliative RT (20Gy/5#) and
inj. zolidronic acid.
Results: 2/9 had significant pain reduction, 6 had partial response to
pain while 1 patient had minimal response to pain as assessed by VAS
scale.
Conclusion: Pain at sternal metastasis to a certain extent can be
taken care of with the palliative radiation therapy and/or zolidronic
chemotherapy but the exact etiopathogenesis, prevention protocols
and definitive modality of treatment in inoperable cases of sternal
metastasis still needs to be explored and discussed.
S57
administered following the European Standard Operative Procedures of
Electrochemotherapy. Tumor response was clinically assessed adapting
the Response Evaluation Criteria in Solid Tumors (RECIST) and toxicity
was evaluated according to CTAE 4.0. Cox regression analysis was used
to identify predictive factors.
Results: Tumor response was evaluable in 113 patients for a total of 214
tumors (median 1/patient, range 1−3). The overall response rate after
two months was 90.2%, while the complete response (CR) rate was
58.4%. In multivariate analysis, small tumor size (P<0.001), absence
of visceral metastases (P=0.001), estrogen receptor (ER) positivity
(p=0.016), and low Ki-67 index (P=0.024) were significantly associated
with CR. In the first 48 hours, 10.4% of patients reported severe skin pain.
Dermatological toxicity included G3 skin ulceration (8.0%) and G2 skin
hyperpigmentation (8.8%). One-year local progression-free survival was
86.2% (95% CI 79.3-93.8) and 96.4% (95% CI 91.6−100) in the subgroup of
complete responders.
Conclusions: In this study, small tumor size, absence of visceral
metastases, ER-positivity, and low Ki-67 index were predictors of CR
after ECT. Patients who achieved CR experienced durable local control.
ECT represents a valuable skin-directed therapy for selected patients
with BC.
PO104
THE SURGICAL MANAGEMENT OF LUNG NODULES IN BREAST CANCER
PATIENTS
Kazuo Matsuura1, Midori Noma1, Ryosuke Arata1, Keiso Matsubara1,
Satoshi Sueoka1, Masateru Yamamoto1, Ryuta Ide1, Toshiyuki Itamoto1,
Takayuki Kadoya2, Morihito Okada2, Koji Arihiro2
1
Hiroshima Prefectural Hospital, Breast Surgery, Hiroshima, Japan;
2
Hiroshima University Hospital, Breast Surgery, Hiroshima, Japan
Clinical Issues: Surgical Oncology
BP103
ELECTROCHEMOTHERAPY IN THE TREATMENT OF CUTANEOUS
METASTASES FROM BREAST CANCER: A MULTICENTER COHORT
ANALYSIS
Roberto Agresti8, Carlo Cabula11, Luca Campana14, Gretha Grilz2,
Riccardo Bussone2, Sara Galuppo14, Sara Valpione14, Leonardo De Meo4,
Antonio Bonadies12, Pietro Curatolo10, Michelino De Laurentiis13,
Maria Renne3, Tommaso Fabrizio6, Nicola Solari5, Michele Guida7,
Antonio Santoriello1, Massimiliano D’Aiuto9
1
“Federico II” University, Department of Medicine and Surgery, Napoli,
Italy; 2A.O.U. Città della Salute e della Scienza, Breast Surgery Unit,
Torino, Italy; 3Fondazione T. Campanella, Oncologic Surgery, Catanzaro,
Italy; 4Humanitas-Centro Catanese di Oncologia, Oncologic Surgery,
Catania, Italy; 5IRCCS San Martino-IST, Surgical Unit 1, Genova, Italy;
6
IRCCS, Referral Cancer Center of Basilicata, Plastic Surgery Unit, Rionero
in Vulture, Italy; 7Istituto dei Tumori, Medical Oncology Unit, Bari, Italy;
8
Istituto Nazionale dei Tumori, Breast Surgery Unit, Milano, Italy; 9Istituto
Nazionale Tumori “Pascale”, Breast Surgery Unit, Napoli, Italy; 10La
Sapienza University, Dermatology and Plastic Surgery Department, Roma,
Italy; 11Ospedale Oncologico A. Businco, Oncologic Surgery, Cagliari, Italy;
12
San Gallicano Dermatologic Institute, Plastic Surgery Unit, Roma, Italy;
13
Seconda Università di Napoli, Medical Oncology, Napoli, Italy; 14Veneto
Institute of Oncology IOV-IRCCS, Oncologic Surgery, Padova, Italy
Background: The management of breast cancer (BC) skin metastases
represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin (BLM), a poorly permeant
cytotoxic agent, with temporary permeabilization induced by locallyadministered electric pulses. Preliminary experience with ECT in BC
patients is encouraging.
Patients and Methods: 125 patients with BC and skin metastases, who
underwent ECT at 13 Italian centers between 2010 and 2013, were
enrolled in a multicenter retrospective cohort study. The treatment was
Background: A biopsy of lung nodules in patients, who had received
previous surgery for breast cancer, can be performed with three aims:
to confirm that the lesion is lung metastasis, to confirm the diagnosis
of other diseases including primary lung cancer, and to reassess the
biological features of recurrent tumors. Discordance in estrogen receptor
(ER), progesterone receptor (PR) and human epidermal growth factor
receptor 2 (HER2) status between primary breast cancer and metastatic
lesions has been reported. The aim of this study was to evaluate the role
of lung biopsy in the diagnosis and to reassess the changes in tumor
phenotype of lung metastases.
Methods: A total of 53 consecutive patients who underwent surgery in
45 or lung biopsy in 8 for lung nodules at two institutions between 1997
and 2014 after curative operation for breast cancer were retrospectively
reviewed.
Results: The pathologic diagnoses of lung nodules were lung metastases of breast cancer in 25 patients, primary lung tumor in 21
(adenocarcinoma in 17; large cell carcinoma in 2; small cell carcinoma
and carcinoid tumor in 1 each), and other diagnoses in 7 (Inflammation
in 4; organizing pneumonia in 2 and hamartoma in 1). Median follow
up duration were 117.9 months in metastatic breast cancer patients and
93.2 months in other histology patients (p=0.103). The average diseasefree interval from the treatment for primary breast cancer were 66.3
months in metastatic breast cancer patients and 52.7 months in other
histology patients (p=0.325). The 3-year survival rate after the lung
biopsy were 84.2% in metastatic breast cancer patients and 91.7% in
other histology patients (p=0.436). Of all cases, 30 patients (57%) had
a single lung nodule. The 3-year survival rate after the lung biopsy was
significantly longer in patients with single nodule (100%), including
primary lung cancer patients, than in patients with multiple nodules
(71.9%) (p=0.00341). Of 25 cases of metastatic breast cancer, 17 patients
maintained the same tumor phenotype, whereas discordance of ER,
PR, HER2, and Ki67 expression was observed between primary sites
and metastatic sites in 6 (24%), respectively ER gain, 2; PR gain, 1; Ki67
gain, 1 and HER2 loss, 2. Especially, 3 cases of ER, PR gain could receive
endocrine therapy instead of chemotherapy.
Conclusion: As lung nodules that appear in breast cancer patients are not
always lung metastases, the pathologic diagnosis should be confirmed,
S58
Abstracts / The Breast 24 S3 (2015) S21–S75
and surgery is an option for the pathologic confirmation. Furthermore,
discordance in tumor phenotype from primary breast cancer to matched
lung metastasis occurred in 24% of cases. It is necessary for clinicians to
check biomarker profile in recurrent breast cancer patients as it may
assist a shift in the treatment plan.
PO105
SUCCESS AND FAILURE OF PRIMARY MEDICAL, NON-OPERATIVE
MANAGEMENT IN PATIENTS WHO PRESENT WITH STAGE IV BREAST
CANCER
Uwe Güth2,5, Dorothy Huang5, Andreas Schötzau3, Seraina Schmid4,1
1
Breast Center St. Gallen, Spital Grabs, Grabs, Switzerland; 2Cantonal
Hospital Winterthur, Breast Center “Senosuisse“, Winterthur, Switzerland;
3
Eudox, Institute for Biomathematics, Basel, Switzerland; 4Spital Grabs,
Gynecology & Obstetrics, Grabs, Switzerland; 5University Hospital Basel,
Gynecology & Obstetrics, Basel, Switzerland
Introduction: There is a long-standing controversy as to whether
there is benefit to resecting the primary tumor in patients who present
with stage IV breast cancer (BC). Many retrospective studies have
demonstrated significant survival advantage in patients who underwent
surgery; on the other hand, two prospective randomized trials failed
to confirm these results. However, survival is only one component in
a non-operative approach. If patients and physicians agree on nonoperative treatment as initial management, this decision is made on
the assumption that the patient’s life expectancy is limited and that
long-term control of locoregional disease can be achieved with systemic
therapy only. Thus, success of a non-operative management might also
be reached independent of survival time when one major aim of this
approach is reached: the avoidance of clinically relevant locoregional
progression during the further disease course. We evaluate the rates of
and predictive factors for success and failure of this particular therapy
approach.
Methods: Forty-four patients with stage IV BC, diagnosed between
1990 and 2009 at the University Women’s Hospital Basel, Switzerland,
who were initially treated only systemically and in whom local control
while avoiding surgery was the intended long-term therapy goal were
analyzed. Failure of therapy was defined when a) secondary surgery
had to be performed due to locoregional progression; or b) in case of
no surgery, severe locoregional clinical signs/symptoms were observed
during the further course of the disease. The study cohort had a median
age of 67.5 years at diagnosis. The median MDS survival was 24.5
months.
Results: Most patients responded positively after starting medical
treatment (n=34, 77.3%). In six patients (13.6%), secondary surgery had
to be performed. In the cases where no surgery was performed (n=38),
14 women (36.8%) suffered from severe locoregional symptoms in
the further disease course. In total, our defined therapy goal of nonoperative but systemic therapy as first-line management was not met
in 20 patients (45.5%). Overall survival time (p=771), hormone receptor
status (p=1.00) and the number of metastatic sites (p=1.00) had no
impact on therapy success. Older patients and those with larger tumors
had a trend toward failure of therapy (both p=0.076); non-inflammatory
skin involvement was significantly associated with failure of therapy
(p=0.035).
Discussion: Non-operative treatment may be offered to BC patients
with primary metastatic disease. The patients must be informed that,
with regard to survival, the impact of this approach is still unclear; but
nevertheless, is not successful in more than 40% of the cases with regard
to local control.
PO106
N2 LYMPH NODES POST-PRIMARY CHEMOTHERAPY MAY PREDICT
RECURRENCE IN LOCALLY ADVANCED BREAST CANCER
Carol Ann Benn1,3, P. Mapunda3,2, S. Rayne1,3
1
Helen Joseph Breast Care Clinic, Johannesburg, South Africa; 2University of
Edinburgh, Edinburgh Surgical Sciences Qualification, Edinburgh, United
Kingdom; 3University of the Witwatersrand, Faculty of Health Sciences,
Department of Surgery, Johannesburg, South Africa
Background: Locally advanced breast cancer at initial presentation is
a common entity in South Africa. Historically almost all patients with
big T4 breast cancers were categorized as inoperable. Advances in
oncology therapies and in reconstructive techniques have enabled us
to downstage these tumours and render them operable. Timing and
benefit of surgery on durable local control should be better defined
particularly in relation to factors which may predict early recurrence.
This study looked retrospectively at the relationship between clinical
factors, neo-adjuvant treatment response and early local or systemic
recurrence. Through this we hope to better select the patients who will
benefit from comprehensive local excision and the timing of surgery in
relation to oncology treatment.
Methods: This was a retrospective records review over a three-year
period of patients diagnosed with T4 breast cancer at the Helen Joseph
Breast Care Clinic based in a government hospital in Johannesburg,
South Africa. All patients diagnosed histologically with an invasive
breast cancer of any subtype presenting with the clinical stage T4NxMx
were included (nodal status and metastases are not in the recruitment
criteria). Medical records were reviewed for demographics, clinical
and radiological characteristics, and histology. Response to treatment
outcome was also documented.
Results: Of the 87 patients who were included with a T4 (NxMx)
diagnosis, 65 were black (74.7%), 13 were white (14.9%), 6 Indian (6.9%)
and 3 coloured (3.4%). Median age at presentation was 62 years (range:
31-103 years). 11 patients had loco-regional recurrences. They all
received primary chemotherapy and were deemed clinically resectable.
9 out of the 11 were alive 18 months post surgery. Chemotherapy
protocols involved either 6AC, or AC T. 10/11 of the patients who
reoccurred had N2 lymph nodes on final histology. The histology of the
recurrences were majority luminal B 8/11.
Conclusion: Timing of surgery in T4 LABC patients may be better
predicted by a focused nodal ultrasound prior to decision to operate or
continue chemotherapy in clinical responders. These patients benefit
from surgery but a significant rate of recurrence (one quarter in this
study) should be expected. Nodal disease burden may be an accurate
indicator of recurrence in this group.
PO107
SURGICAL RESECTION OF THE PRIMARY TUMOR IS ASSOCIATED
WITH INCREASED LONG-TERM SURVIVAL IN PATIENTS WITH STAGE
IV BREAST CANCER
Anna Sukhotko, A. D. Zikiryahodjaev, L.V. Bolotina, A.A. Volchenko
Moscow P.A. Gerzen’s Cancer Research Institute – The National Medical
Research Radiologic Center of the Ministry of Health of the Russian
Federation, Department of Oncology and Reconstructive-plastic Surgery of
the Breast and Skin, Moscow, Russian Federation
Purpose: To evaluate the expediency and timeliness of performance
of surgical treatment as a component of multi-therapy treatment of
patients with stage IV breast cancers.
Materials and Methods: This investigation comparatively analyzed
the results of complex treatment with or without surgery in patients
with metastatic breast cancer. We analyzed retrospectively treatment
experience of 196 patients with generalized breast cancer in the
department of oncology and breast reconstructive surgery of P.A.
Herzen Moscow Cancer Research Institute from 2000 to 2012. Average
age was (58±1.1) years. Invasive ductual carcinoma was verified in 128
Abstracts / The Breast 24 S3 (2015) S21–S75
patients (65.3%), invasive lobular carcinoma - 33 (16.8%), complex form 19 (9,7%). Complex palliative care involving drug and radiation therapies
was performed in two patient groups. The first group includes 124
patients who underwent surgical intervention as complex treatment,
the second group includes 72 patients with only medical therapy.
Standard systemic therapy was given to all patients.
Results: Overall, 3-and 5-year survival in fist group was 43.8 and 21%,
in second - 15.1 and 9.3% respectively [p=0.00002 log-rank]. Median
survival in patients with surgical treatment composed 32 months, in
patients with only systemic therapy - 21. The factors having influencing
an influence on the prognosis and the quality of life outcomes for of
patients with generalized breast cancer were are also studied: hormonedependent tumor, Her2/neu hyper-expression, reproductive function
status (age, menopause existence).
Conclusion: Removing primary breast tumor in patients with
generalized breast cancer improve long-term outcomes. Three- and
five-year survival increased by 28.7 and 16.3% respectively, and median
survival – for 11 months. These patients may benefit from resection of
the breast tumor. One explanation for the effect of this resection is that
reducing the tumor load influences metastatic growth.
PO108
NOVEL AND SAFE TECHNIQUES IN IMMEDIATE BREAST
RECONSTRUCTION FOR LOCALLY ADVANCED BREAST CANCER,
PARTICULARLY INFLAMMATORY BREAST CANCER
Marisse Venter, C.A. Benn, S.D. Moodley, S. Nayler
Breast Care Center of Excellence, Breast Oncology, Johannesburg, South
Africa
Introduction: Locally advanced breast cancer poses unique surgical and
reconstructive dilemmas both in terms of oncological safety, and patient
quality of life. Studies involving reconstruction are few, and most units
do reconstruct immediately if local surgery is performed. In our unit we
perform a two part surgery spaced 48 hours apart in order to facilitate
immediate reconstruction in these patients.
Aims: Our aim is to demonstrate that breast reconstruction is possible
in advanced breast cancer thus improving patient quality of life.
Methods: We performed a prospective study of patients with locally
advanced breast cancer and inflammatory breast cancer treated in our
unit from October 2013 to August 2015. Patients with inflammatory
breast cancer, extensive DCIS with invasion and nodal disease, unknown
primary disease were included in the study. Standard oncological
protocol for locally advanced breast cancer (primary chemotherapy)
was observed. We evaluated the patient demographics, pre and
postoperative histological features, tumour biology, oncological and
reconstructive procedures and cosmetic outcomes.
Results: 78 patients were referred to a single reconstructive surgeon
during this period; 2 patients had bilateral breast cancer, 21%
inflammatory cancers, 8% unknown primary, 37% multi-centric disease,
17% extensive DCIS, with invasive and nodal disease and 17% large
tumors post primary chemotherapy. The average patient age was 47
years. All patients received radiation post surgery. Chemotherapy
protocols were initially decided in the MDM. The majority of patients
underwent reconstruction to the affected breast with an opposite side
matching procedure. The average duration of the first procedure was
25 min and the reconstructive procedure was 133 min. Surgery and
reconstructive outcomes were evaluated photographically. More than
50% of patients had a complete histological response.
Conclusion: Breast reconstruction is possible in locally advanced breast
cancer. The immediate delayed reconstruction provides reconstruction
in patients who were previously only offered delayed reconstruction, if
at all. The procedure allows for adequate histological assessment and
clear margins prior to immediate reconstruction and facilitates a better
cosmetic result. Advances in chemotherapeutic regimes have improved
the survival of these patients and breast reconstruction improves their
quality of life.
S59
PO109
THE IMPACT OF LOCOREGIONAL TREATMENT OF PRIMARY
METASTATIC BREAST CANCER
Roman Liubota2, Roman Vereshchako2, Valeriy Cheshuk2,
Mykola Anikusko1, Iryna Liubota1,2
1
Municipal Clinical Oncological Centre, Municipal Clinical Oncological
Centre, Kyiv, Ukraine; 2National Medical University named after O.O.
Bogomolets, Oncology Department, Kiev, Ukraine
Background: Systemic therapy is usually the main treatment for
patients with primary metastatic breast cancer (PMBC) and use of others
radical methods, such as surgery or radiotherapy, in palliative care are
controversial. The aim of this study was to investigate the impact of
primary tumor locoregional treatment (surgery or/and radiotherapy) on
overall survival of patients with PMBC.
Patients and Methods: The study included women aged 23 to 76
(55.4 ± 0.6) years old, who lived in Kiev at the time of diagnosis
with PMBC from 2000 to 2010. Among the 295 patients, the effect of
locoregional treatment of primary tumor on survival outcomes was
evaluated in 177 women with distant metastases at diagnosis of breast
cancer. 35 patient received breast surgery (group 1), 95 women’s with
PMBC gotten radiotherapy (group 2) and 47 patients - combination of
breast surgery and radiation (group 3). The remaining 118 patients don’t
received surgery or/and radiotherapy (group 4). All patients received
systemic cytotoxic chemotherapy. The median follow-up period was
22.3 ± 1 months (range, 1–91 months). The Kaplan-Mayer method was
used to estimate the patient’s survival rate.
Results: In patients of study groups was no significant difference
for age, menstrual function, ER status, HER2 receptor status, site of
metastases and number of metastatic lesions. 2 and 5-year overall
survival in patients of group 1 was 54% and 32%, group 2 – 47% and
8%, group 3 – 73% and 18%, whereas those of patients of groups 4
were 26% and 9%, respectively. The median survival for patients who
underwent surgery was 36 months, women’s with PMBC who received
radiotherapy – 24 months, patients who treated combination of breast
surgery and radiation was 30 months versus 18 months in patients who
have not received primary tumor locoregional treatment (surgery or/
and radiotherapy).
Conclusions: The results of this study show the positive impact of
locoregional treatment on the prognosis of patients with PMBC.
However, further research should be aimed at establishing criteria for
selecting patients with primary metastatic breast cancer for primary
tumor locoregional treatment (surgery or/and radiotherapy).
PO110
METASTASES OF LOBULAR BREAST CARCINOMA IN THE TERMINAL
ILEUM AND ILEOCAECAL VALVE
Sala Abdalla, Peter Macneal, Cynthia-Michelle Borg
University Hospital Lewisham, Department of General Surgery, London,
United Kingdom
Gastrointestinal (GI) metastases from primary breast carcinoma are rare
but more common in invasive lobular carcinoma than invasive ductal
carcinoma. The symptoms may be non-specific and the presentation can
occur many years after the initial primary breast carcinoma. Radiological
and endoscopic findings can be difficult to distinguish from inflammatory
bowel disease and primary carcinoma of the GI tract. Histological and
immunohistopathology assessment will usually confirm the diagnosis
of metastatic breast carcinoma. We report the first case of lobular breast
carcinoma metastasizing to the terminal ileum and ileocaecal valve 19
years following treatment for breast cancer in an 82-year-old woman.
Staging investigations revealed synchronous metastases in bones and
the pleura. A high index of suspicion and awareness of the potential long
interval in the presentation of metastatic breast cancer help in making
an accurate diagnosis and rapid clinical management.
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PR111
SURGICAL TREATMENT OF ADVANCED BREAST CANCER. URGENCY OF
THE PROBLEM
Michail J. Myasnyankin
Federal State Budget Institution, Oncology Scientific – research Institute
named after N.N. Petrov, Dept. of General Oncology, St. Petersburg, Russian
Federation
Purpose: Determination of the effect surgery on the results of complex
treatment of patients with advanced breast cancer (breast cancer).
Material and Methods: The study included 196 patients treated in
the department from 2000 to 2012 diagnosis was made according to
the International TNM-classification (7th ed., 2011): Tl Nl M1 - The
presence of distant-metastases. The study included women aged 32-80
(58 ± 1,1) years. Frequently diagnosed with invasive ductal carcinoma
-128 (65.3%) and invasive lobular carcinoma - 33 (16.8%), and combined
forms of ductal lobular cancer - 19 (9.7%), a rare form of cancer -16 (8.2%)
patients. As a result of study patients were divided into 2 groups. In
group 1 (n = 124) included patients who surgery is performed in terms
of complex treatment, in group 2 (n = 72) - large , SPECIAL undergoing
only conservative treatment. Surgery patients Group 1 performed in the
volume of palliative mastectomy. In the first stage surgical vme-vention
on the primary focus was performed in 16 (12.9%) patients due to the
risk of bleeding, often vital reasons. In 108 (55.1%) patients, in addition
to the removal of the primary tumor. You are use 3-r lymphadenectomy.
Results: Overall 3- and 5-year survival rate Group 1 patients was 51.0
and 36.2%, while as the 2 groups of patients - 15.0 and 7.9% respectively
(p<0.05). The median duration of life for patients who have not
performed surgical intervention was 24 months against 42 months in
patients who underwent palliative operation. The most common distant
metastasis dosing was recorded at a tumor G2 that was more than 2
times higher in comparison with tumors of the G1.
Conclusions: Surgical removal of the primary focus in the breast in
patients advanced breast cancer significantly enhances treatment
cheniya and improve the prognosis of the disease. In women who
underwent palliative mastectomy, 3- and 5-year survival increased by
36% and 29% respectively, while the length life - 18 months, compared
with patients conservative treatment.
Clinical Issues: Supportive and Palliative care
PO112
EFFICACY OF NEPA, THE FIRST COMBINATION ANTIEMETIC AGENT,
IN PATIENTS WITH BREAST CANCER RECEIVING ANTHRACYCLINE/
CYCLOPHOSPHAMIDE (AC) OR NON-AC CHEMOTHERAPY
Hope Rugo3, Matti Aapro1, Giorgia Rossi2, Giada Rizzi2
1
Clinique de Genolier, Medical Oncology, Genolier, Switzerland; 2Helsinn
Healthcare, Clinical Development & Biostatistics, Lugano, Switzerland;
3
University of California San Francisco Comprehensive Cancer Center,
Hematology/Oncology, San Francisco, USA
Background: Patients with breast cancer (BC) are at high risk for
developing chemotherapy-induced nausea and vomiting (CINV) due
to the intrinsic emetogenicity of the chemotherapy (often AC-based)
and also the predisposing risk factors of young age and female gender.
Antiemetic guidelines recommend prophylactic co-administration
of an NK1 receptor antagonist (RA), a 5-HT3RA, and dexamethasone
(DEX) for these patients. NEPA is an oral fixed combination of a new
NK1RA, netupitant (300 mg), and palonosetron (PALO 0.50 mg), a
pharmacologically and clinically distinct 5-HT3RA. In a large phase 3
trial, NEPA + DEX was superior to oral PALO + DEX in preventing CINV
in patients receiving AC-based chemotherapy (Aapro, Annals Oncology
2014). The objective of this post-hoc analysis was to evaluate the efficacy
of NEPA in the subset(s) of patients with BC from this Aapro trial as
well as from a separate trial in patients receiving non-AC chemotherapy
(Gralla, Annals Oncology 2014).
Methods: Data was compiled for the subsets of BC patients receiving
NEPA from two randomized, double-blind, pivotal registration trials.
Patients in both trials received a single dose of NEPA prior to AC in Study
1 or non-AC based chemotherapy in Study 2. A single dose of oral PALO
was a comparator in Study 1. All patients also received oral DEX 12 mg
(NEPA-treated) or 20 mg (PALO-treated) on day 1 only. Efficacy endpoints
were complete response (CR: no emesis/no rescue medication) and no
significant nausea (max <25 mm on 100 mm visual analog scale) rates
during the overall phase (0-120h) following chemotherapy. Comparisons
between groups in Study 1 were performed using a Cochran-MaentelHaenszel test.
Results: 1451 patients with BC were included [AC (Study 1): NEPA N =
708, oral PALO N = 704; non-AC (Study 2): NEPA N = 39] for a total of
6016 cycles. In BC patients receiving AC, NEPA was superior to oral
PALO for both overall CR (74% NEPA vs 66% oral PALO, p = 0.001) and no
significant nausea (74% NEPA vs 69% oral PALO, p = 0.016) during cycle
1. Continued superiority of NEPA over oral PALO (p < 0.001) was seen in
each subsequent cycle (NEPA vs oral PALO: cycle 2 - 80% vs 66%; cycle
3 - 84% vs 70%; cycle 4 – 84% vs 74%). The cycle 1 CR rate for NEPA in the
smaller subset of patients receiving non-AC chemotherapy was 85% and
the no significant nausea rate was 87%; CR rates were maintained over
subsequent cycles (cycles 2-4: 94%, 94%, 100%).
Conclusions: NEPA, an oral combination antiemetic targeting two
critical pathways associated with CINV, offers a highly effective and
convenient option for preventing CINV in BC patients at high emetic
risk, receiving either AC or non-AC-based chemotherapy.
PR113
COMPARATIVE ASSESSMENT OF ANALGESIC THERAPY IN PATIENTS
WITH BREAST CANCER IN THE TERMINAL STAGE
Zulaykho Kadirova, Dono Makhamedjanov
Tashkent Medical Academy, High Educated Nurse, Tashkent, Uzbekistan
Narcotic analgesics is still not lose their significance. However, nonnarcotic drugs began to compete with them. But the effectiveness and
duration of narcotic drugs exceed narcotic. It is worth noting that nonnarcotic drugs have a very low degree of addiction and therefore are not
included in the list of narcotic substances.
Objective: To determine the efficacy and duration of narcotic and
narcotic analgesics in patients with breast cancer with bone metastases.
Material and Methods: We studied patients with breast cancer
with bone metastases. All patients had end-stage cancer, verified on
histology. All patients received 2-3 courses of palliative chemotherapy +
biphosphonates and were examined at the current level of pain on a
10-point visual analog scale control. We studied three groups of patients.
Group 1 consisted of 6 people. In this group for pain, we used morphine
1% -1mg under skin. It was noted that this drug had an inhibitory effect
on conditioned reflexes, it depresses the respiratory center, decreased
summering ability of central nervous system, decreased excitability of
the cough center, and also raised tonus of smooth muscles of internal
organs, at the same time weakened peristalsis, which led to the
development of constipation. The drug is in effect for 5-7 hours.
Group 2 consisted of 7 people. This group was used nalbufen 10 mg
intramuscularly. Studies have found that the drug inhibits the central
nervous system, has analgesic, sedative, antitussive effect, affects the
higher parts of the brain and changes the emotional pain. And also, to a
lesser extent than morphine, depressed respiratory center and does not
affect the motility of the intestine. The drug is in effect for 6-8 hours.
3rd group was 6 people. We used NSAIDs (ketoprofen) 2 mg
intramuscularly. As a result, it was found that the drug is detrimental
effect on the rheology of the blood, increased blood clotting time and
caused pain in the epigastric region. The drug is in effect for 1-3 hours.
Results: Comparing the effect duration from three study groups nalbufen
efficiency better than others and there was no serious side effects and
withdrawal symptom. The first group of patients after taking the drug at
all observed constipation and sharp deterioration of appetite. The first
Abstracts / The Breast 24 S3 (2015) S21–S75
and the second group in a blood test no change observed. In group 3
lower efficiency than the others, and in blood changes were observed.
Conclusions: From the studies it was found that the terminal stage
breast cancer with metastases is preferable to use nalbufen. Since the
drug is not addictive, it lasts longer than morphine and NSAIDs and has
far fewer side effects than other drugs of the above groups. Patients in
the thermal stage, it is not recommended to use NSAIDs as analgesic.
PO114
USING OF HEPATOPROTECTORS IN THE DRUG TREATMENT OF
PATIENTS WITH ADVANCED BREAST CANCER
Jamshid Ibragimov, Doniyor Pulatov
National Cancer Research Center, Chemotherapy Department, Tashkent,
Uzbekistan
Antineoplastic chemotherapy agents are occupying leading positions in
frequency and severity of induced hepatotoxic reactions.
Purpose: Improve the results of treatment of cancer by selecting
adequate hepatoprotectors.
Material and Methods: In period of 2012-2014 years in the
chemotherapy department of Cancer Research Center of Uzbekistan,
were observed 57 patients with advanced breast cancer who underwent
neoadjuvant and adjuvant polychemotherapy by TAC regimen. Patients
were divided into 3 groups: control group (n = 20) received only
polychemotherapy, patients in group 2 (n = 18) during and after the
cycle was assigned a combined preparation with hepatoprotective
activity of plant origin. In the third group - 19 patients in addition to
the cancer drug treatment, the period between cycles, was administered
S-ademetionine (Heptral®) intravenously 400 mg 2 times a day for 5
days followed by oral use. Monitoring liver function was carried out by
studying the levels of markers of cholestasis syndromes and cytolysis
and periodically ultrasound study of structural changes.
Results: Signs hepatotoxicity recorded considerable and significantly
less in the group receiving S-ademetionine, and its severity was
significantly lower than in the other two groups. In 9 (45%) patients of the
comparison group and 8 (44.4%) patients in group 2 noted a persistent
and progressive increase in transaminases, causing lengthening of the
interval and the reduction of dose chemotherapy. In the group receiving
S-ademetionine, treatment protocol violations were only 1 (5.2%)
cases. It showed a significant reduction such markers of cytolysis and
cholestasis of AST and ALT, total bilirubin by the end of treatment with
S-ademetionine. ALP and LDH levels also tended to decrease.
Conclusion: The obtained data lead to the conclusion a high incidence
of drug-HT during chemotherapy in cancer patients. They strongly
require corrective cover treatment between cycles by assigning of
hepatoprotectors.
PO115
THE EMOTIONAL TOLL OF METASTATIC BREAST CANCER ON YOUNG
WOMEN
Medha Sutliff, Desiree Walker, Michelle Esser, Megan McCann, Jean Rowe
Young Survival Coalition, National Programs, New York, USA
Background and Methods: Young women (YW) diagnosed with
metastatic breast cancer (MBC) face unique concerns. Young Survival
Coalition (YSC) is the premier global organization dedicated to critical
issues particular to YW and breast cancer. In 2012, YSC engaged in a two
year long process called the Research Think Tank (RTT) to determine
the most pressing research questions in need of answers. The RTT
found that research into MBC in YW was rare and determined that a top
research priority was “How can we better meet the psychosocial needs
of YW with MBC and their families?”. After identifying this priority,
from September 2013 to February 2014 YSC conducted an online survey
of women diagnosed with any stage of breast cancer before age of 41,
who either had MBC at initial diagnosis or developed it thereafter.
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Results: Four hundred seventy participants met the inclusion criteria
with 360 YW completing the entire survey. Results showed that since
their MBC diagnosis, their stress level is worse (31%) or varies (56%),
with some days stressful and some not. Emotional wellbeing worsened
in 57%. Emotional wellbeing due to MBC was impacted by: anxiety
(71%); trouble sleeping (61%); depression (45%); withdrawal from things
they once liked to do (31%); and withdrawal from friends (24%). Before
their diagnosis, less than one-third had anxiety (28%) or depression
(24%). Eighty-six reported that they take time to rest while 14% said “no”
with guilt, lack of time, lack of willingness to do so and children cited
as causes. Asked if they take time to “do nothing,” 25% said “no,” with
similar reasons cited. Eighty-two percent said that anticipatory grief
was a topic of importance to them. They said they were grieving: loss of
life cut short (86%); leaving spouse or partner (75%); leaving behind kids
without mother (67%); and loss of identity (38%). How can these issues
be addressed? The survey revealed that connecting with other YW living
with MBC to receive support and information is important. Therapy and
counseling were also listed as a helpful source of support for emotional
issues. Suggestions for what could make finding information and
support easier included easy to find on-line information specifically for
YW with MBC as well as physician referrals to support such as social
workers. Seventy-six percent responded that tools to communicate
about their disease and prognosis would be helpful.
Conclusion: YW living with MBC are an understudied population in
need of psychosocial and emotional support and tools. YSC’s survey
sought to understand how to address these issues. Using these survey
results, YSC has revised its metastatic navigator and is updating the MBC
portion of its website.
PO116
THE LAST QUARTER OF A HONEYMOON – A WEDDING’S STORY
Jose Pereira1,2, Vasco Fonseca1, Leonor Fernandes1, Margarida Miguens 1,
Arturo Botella1, Candida Fonseca 2, Ana Martins1, Luis Campos2,
Debora Cardoso1
1
Hospital Sao Francisco Xavier, Oncology Department, Lisbon, Portugal;
2
Hospital Sao Francisco Xavier, Medical Department, Lisbon, Portugal
Introduction: According to the International Agency for Research on
Cancer, there will be an increase on the occurrence of cancer related
diseases, in the coming years. In Portuguese Hospitals there has been a
significant increase of the support attendance to patients with cancer.
The cancer patients’ growth and the consequent pressure on the
Portuguese National Health Service have implied new sceneries and
requirements in which health care is concerned. There are, nevertheless,
issues where the professionals’ correct approach is not completely
defined. One of these situations, uncommon, is the end-of-life wedding.
Clinical Case: We present the case of a fifty year old patient, with a
triple-negative breast cancer, diagnosed in May 2013. She was treated
with a tumorectomy, followed by adjuvant chemotherapy and adjuvant
radiotherapy on the breast. Three months after finishing the adjuvant
therapeutics she was diagnosed with multiple metastases. The biopsy
has confirmed an invasive triple-negative breast carcinoma with
high proliferative index. In May 2014, she initiated chemotherapy for
metastatic disease. As the patient hadn’t got clinical conditions to
perform a specific oncological treatment, a symptomatic palliative
therapeutics was undertaken. The week, prior to her passing, the patient
got married in São Francisco Xavier Hospital, where she was hospitalized
and where she remained until her death.
Discussion: The question of one patient, diagnosed with a tumour of
very aggressive biology, deciding to get married in her last few weeks
of life, has forced us to reflect upon the patients’ needs and priorities,
during this stage, and the urge they have to weigh several aspects of
their lives in a short period of time. It also implies how important it
is the transparency of the communicated information regarding the
pathology’s seriousness, keeping at the same time, a sense of hope. The
multidisciplinary team had faced the need to approach the situation
in all its dimension, managing hopes and emotions, not only from the
patient but also from themselves. The wedding ceremony has taken
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Abstracts / The Breast 24 S3 (2015) S21–S75
place at the hospital, in the presence of family members and staff. The
medical doctors who were invited to the wedding had chosen not to
participate with the main purpose of keeping the emotional distance
that would allow them to make a more rational decision. After the
wedding some of the doctors would consider their presence at the
ceremony from a different perspective.
Conclusion: This case reflects the need of having well prepared and
orientated teams, to approach the patient as a whole in her/his final
life stage, not only to provide the pharmacological symptomatic relief,
but also the emotional comfort, so many times considered as secondary.
PO117
CAN WE MAKE A PORTRAIT OF WOMEN WITH INOPERABLE LOCALLY
ADVANCED BREAST CANCER? THE EXPERIENCE OF THE BREAST UNIT
OF SOUTHERN SWITZERLAND (CSSI)
Giacomo Montagna1,2, Gabriella Bianchi-Micheli2, Lorenzo Rossi2,3,
Marzia Conti-Beltraminelli2,3, Roberta Decio2, Vilma Ratti3,
Thomas Gyr1,2, Olivia Pagani2,3, Francesco Meani1,2
1
Ente Ospedaliero Cantonale, Department of Obstetrics and Gyneacology,
Lugano, Switzerland; 2Ente Ospedaliero Cantonale, Breast Unit of Southern
Switzerland (CSSI), Lugano, Switzerland; 3Ente Ospedaliero Cantonale,
Oncology Institute of Southern Switzerland (IOSI), Bellinzona, Switzerland
Introduction: Breast cancer (BC) is the most common cancer in
women. Early detection and treatment improvements have both led to a
significant decrease in mortality over the last 25 years. Locally advanced
BC (LABC) is defined as large operable primary BC (stage IIB, IIIA) and/or
inoperable BC (i.e. involving the skin/chest wall and/or with extensive
nodal involvement) (stage IIIB, IIIC). Despite the amount of information
available through the media and advocacy groups (i.e. Europa Donna),
repeated events to raise public awareness (i.e. the Pink Ribbon
Campaign) and mammography screening programs, LABC still accounts
for 5-10% of all new primary BC diagnoses. Overall, the prognosis of
patients with LABC is relatively poor with a 5-year overall survival <50%.
Materials and Methods: Between 2008-2014, >1300 patients with a
newly diagnosed primary BC have been treated at CSSI. 114 patients (9%)
had LABC at diagnosis. We planned to retrospectively investigate the
demographic (i.e. age, social and marital status, education level, religious
beliefs) and psychosocial characteristics (i.e. BC family history, somatic
and psychiatric co-morbidities, use of psychiatric therapy, concomitant
chronic diseases, timing of symptom detection and initial symptom
interpretation, emotional reactions, family and social interactions) of
these patients. A demographic survey and a semi-structured interview
(28 items) was specifically developed and submitted by the treating
team (gynecologist, psychologist, medical oncologist) to all consenting
patients.
Aims of the study: With this study we intend to assess the demographic
and psychosocial features of women with LABC treated at our institution
over the past 6 years and possibly identify factors which led them to
delay seeking medical attention. Data are under collection and will be
analyzed and ready to be presented by the end of October 2015. We aim
at drawing a patient’s profile that could be potentially used to better
identify those women who are at higher risk for developing LABC in
our geographic area in order to build specific and targeted information
and awareness tools. On the long term, we want to evaluate the impact
of the mammographic screening program, recently introduced in our
canton, on the incidence of LABC.
PR118
COMPARISON OF INTEGRATIVE CARE EXPECTATIONS BETWEEN
BREAST CANCER PATIENTS AND BREAST ONCOLOGY PHYSICIANS IN
AN ETHNICALLY DIVERSE POPULATION
Damien Hansra3,4, Jeremy Ramdial1, David Ruiz2,3, Ashwin Mehta4,
Eugene Ahn4, Jorge Antunez de Mayolo3
1
Jackson Memorial Hospital, Oncology, Miami, USA; 2Mast Academy,
Oncology Clinical Research, Miami, USA; 3Mercy Hospital/Oncology and
Radiation Associates, Hematology & Oncology, Miami, USA; 4Sylvester
Comprehensive Cancer Center at the University of Miami, Oncology,
Miami, USA
Purpose: Evidence shows increased patient utilization of various
integrative care modalities to manage symptoms and improve quality
of life. Measurements of breast cancer patients and physicians’ opinions
regarding the importance of integrative care are lacking. We aim to
compare how integrative care modalities are values between physicians
and patients.
Methods: University of Miami IRB obtained. Adult breast cancer
patients (pts) and physicians who specialize in breast cancer (MDs) at an
academic tertiary care medical center in Miami, Florida were enrolled to
complete a survey. Inclusion criteria: adult cancer pts and treating hem/
onc MDs. Exclusion criteria: Pts without breast cancer and non-breast
cancer specialist MDs. Demographics include: age, gender, race, and
ethnicity. Clinical info included cancer subtype and MD name. Survey
had 7 questions assessing opinions on “comprehensive care”, asking
“In addition to standard care, it’s important to incorporate/provide”
nutrition services, exercise therapy, spiritual/religious counseling,
supplement/herbal advice, support groups, music therapy, or other
complimentary medicine services (acupuncture, massage, relaxation
therapy). Data recorded on a 5 point Likert scale (1 = highly disagree,
2 = disagree, 3 = neutral, 4 = agree, 5 = highly agree) and made into 2
categories (1, 2, 3 = neutral/disagree vs. 4, 5 = agree). Fisher’s exact test
with 2 sided p-value used to compare responses between MDs and pts.
Results: 909 pts and 55 MDs enrolled from 06/2013-01/2015 with 144
pts and 11 MDs meeting criteria. Mean pts age = 50 with range 26-88 with
2% male and 98% female. 65% of pts were Hispanic vs. 35% non-Hispanic.
78% were white, 6% black, 0% Asian/Pacific Islander, and 16% other. 71%
of pts agree spiritual/religious counseling is important to incorporate
into cancer care compared to 25% of MDs, p=0.01. Disparities were also
seen for supplement/herbal therapies (90% vs. 36% resp., p=0.001),
music therapy (63% vs. 11% resp., p=0.003), and “other complementary
services” (84% vs. 44% resp., p=0.01). No differences were found for
nutritional advice (88% pts vs. 82% MDs, p=0.63), exercise therapy (90%
vs. 82% resp., p=0.31), and support groups (75% vs. 75% resp., p=1.00).
Conclusion: The majority of adult breast cancer pts seen at a major
academic institution feel that it is important to incorporate nutrition
advice, exercise therapy, spiritual/religious counseling, supplement/
herbal advice, support groups, music therapy, and other complimentary
services as part of their treatment plan. With the exception of support
groups, exercise therapies, and nutritional advice, MDs tend to value
integrative modalities significantly less than pts. Increased availability
and utilization of integrative modalities could improve pts quality of
life, and other clinical endpoints.
PR119
SENSITIZING PRIMARY HEALTHCARE WORKERS TOWARDS
PSYCHOSOCIAL ISSUES OF BREAST-CANCER PATIENTS
S. Pramod
Health Alert Organisation of India, Health Dpt., Garud colony, Deopur,
Dhule, India
Introduction: Primary healthcare workers are backbone of rural/tribal
areas healthcare-sector must be trained for psycho-social needs of
young breast-cancer patients.
Abstracts / The Breast 24 S3 (2015) S21–S75
Objectives: To determine percentage of primary healthcare workers
[PHCW] who would a) give psycho-social/nursing care during their work in
villages. b) refer breast-cancer patients for simple nursing care to specialty
centers owing to their apprehensions or lack of confidence, during their
practice. c) overcome stigma from society/community d) opt for specialized
training to provide supportive care to breast-cancer patients.
Methodology: pre-tested questionnaire given to 52 primary-healthcareworkers from rural/tribal centers of India. Objectives was to answer
anonymously, give suggestive opinion for modification of their current
training program. Data analysed by simple descriptive-statistics.
Results: 21% PHCW would provide psycho-social-support; 79% would
refer them to specialty centers; 75% feared social ostracism/boycott/
stigma; only 7% showed willingness to undergo special care trainingprogram.
Conclusion: Majority of PHCW fear social stigma for associating with
young breast-cancer patients leading to unnecessary referral for routine
issues like nursing care and psychotherapy support. This will result in
difficult access to treatment and avoidable burden on specialty centers.
We need to sensitize nursing personal during these issues. ABC3conference must develop agenda on this matter of training in developing
nations. Cancer-NGO can play vital role in this.
S63
Method: Initially a plan was generated regarding management of an
advanced cancer patient in a nodal centre at District Head Quarter.
Subsequently every two week a trained social worker attached to nodal
centre will follow up and give necessary advice and emotional support
to the patients and their families through their registered mobile phone
number. Patient’s family were also encouraged to communicate with
the team by phone in case of fresh complain and urgency in between.
Results: Since initiation in January 2013, 193 cancer patients were
contacted by mobile phone every two weeks to enquire about their
difficulties. In 76% of the situation trained social workers could give
necessary advice by phone regarding management of their physical
symptoms. Moreover patient’s family were really overwhelmed by the
emotional support offered by the team over phone. Only 24% of cancer
patients has to attend the nodal centre for expert advice from palliative
care specialists.
Conclusion: This novel approach helped:
•
In providing regular physical and emotional support to the patients
and their families.
•
In significantly reducing the financial and manpower problems of
carrying patients to the nodal units.
•
In improve the quality of life of patients by continuous guidance.
More and more team members can take help of this new strategy for
better communication and uninterrupted care.
PR120
DIFFICULTIES IN PROVIDING PALLIATIVE CARE IN RURAL INDIA
(WEST BENGAL) – EXPERIENCE OF AN NGO
Clinical Issues: Other topics
Aditya Manna
MAS Clinic and Hospital, Oncology Dpt., Purba Medinipur, India
PO122
Introduction: As in any developing countries state of West Bengal in
India has a huge burden of cancer patients in advanced stage coming
from rural area where awareness regarding the usefulness of palliative
care in rather poor.
Objective: Our goal is to give a pain free good quality of life in these
advanced stage cancer patients. Objective of this study is to identify the
main difficulties in achieving the above goal in a rural village setting in
India.
Method: Advanced cancer patients in need of palliative care in various
villages in of rural India were selected for this study. Their symptoms
and managements in that rural surroundings were evaluated by an NGO
(under the guidance of a senior palliative care specialist) working in
that area. An attempt was made to identify the main obstacles in getting
proper palliative care in a rural setting.
Results: Pain, fatigue are the main symptoms effecting these patients. In
most patients pain and other symptoms control were grossly inadequate
due to lack of properly trained manpower in the rural India. However
regular homecare visits by a group of social workers were of immense
help in the last few months of life. NGO team was well guided by a
palliative care specialist.
Conclusion: There is a wide gap of trained manpower in this filled
in rural areas of India. Dedicated groups from rural area itself need
encouragement and proper training, so that difficult symptoms can be
managed locally along with necessary social and psychological support
to these patients.
PR121
TELEPHONIC COMMUNICATION IN PALLIATIVE CARE FOR BETTER
MANAGEMENT OF TERMINAL CANCER PATIENTS IN RURAL INDIA –
AN NGO BASED APPROACH
Aditya Manna
MAS Clinic and Hospital, Oncology Department, Purba Medinipur, India
Aim: Due to financial incapability and absence of manpower poor
families often fail to carry their advanced cancer patients to the nodal
centres. This pilot study will explore whether communication by mobile
phone can lessen this burden.
SODIUM FLUORIDE PET/CT: A SUPERIOR IMAGING MODALITY IN
EVALUATION OF OSSEOUS METASTATIC DISEASE
Emily Harrold, Jennifer Murphy, Seamus O’Reilly, Kevin O’Reagan
Cork University Hospital, Medical Oncology Department, Cork, Ireland
Background: Meticulous staging influences treatment decision-making
and is predictive of survival. As the armamentarium of chemotherapeutic
agents expands the importance of increasingly sensitive diagnostic
imaging becomes heightened to ensure appropriate agents are utilised
in a sequence that maximises impact. Technetium-99m methylenediphosphonate bone scintigraphy (Tc-99 MDP BS) is currently the
imaging modality of choice for diagnosis of bone metastases. However
although sensitive it is not specific and is limited in assessment of lytic
lesions. Several studies have shown NaF-18 PET/CT to have greater
specificity, sensitivity and diagnositic accuracy than Tc-99m MDP BS,
MDP SPECT and F-18 FDG PET.
Aim: Na-F-18 PET/CT is available in our centre and has been used to
identify osseous metastatic disease where variance exists between
clinical suspicion and bone scintography or other modalities. We
retrospectively reviewed all breast cancer patients who received NaF-18
PET/CT to assess for osseous metastatic disease.
Methods: A prospectively maintained database was used to identify
all patients who underwent Na-F-18 PET CT between March 2013 and
March 2015. We identified twenty breast cancer patients. Baseline
clinical characteristics, histological features and receptor status were
recorded. The degree of correlation between Na-F 18 PET CT and
comparator imaging was assessed.
Results: Six patients who had suspicious or equivocal Tc-99 MDP BS had
confirmation of osseous metastatic disease with Na-F 18 PET/CT. Seven
patients who had equivocal Tc-99 MDP BS had no osseous metastases
on Na-F 18 PET/CT. Four patients had confirmation of benign osseous
disease by Na-F 18 PET/CT. Two patients who had negative bone scans
but in whom another radiological imaging modality had been suggestive
of metastatic deposits, had no evidence of disease by Na-F 18 PET/CT.
One patient had an indeterminate result on Na F 18 PET CT and biopsy
was advised.
Conclusion: Management of breast cancer patients is evolving and
the integration of increasingly sensitive diagnostic imaging modalities
becomes ever more crucial in order to ensure that therapeutic
decisions are made in a timely fashion in order to deliver the greatest
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Abstracts / The Breast 24 S3 (2015) S21–S75
clinical benefit. Confirmation of metastatic disease has prognostic
implications but also impacts directly on patient’s quality of life from a
symptomatic perspective. Initiation of further chemotherapy, utilization
of bisphosphonates and radiation oncology referral depends on this
confirmation. One third of our patients had bone disease undetectable
on Tc-99 MDP BS. This small case series is suggestive of superiority of
Na-F-18 PET/CT compared with Tc-99 MDP BS and where available it
should be considered to evaluate for osseous metastatic disease.
PR123
PATIENTS’ OWN DECISION ABOUT BECOMING AWARE OF
RECURRENCE EARLIER
Hiroyuki Ishige
Saku Central Hospital Advanced Care Center, Department of Breast
Surgery, Saku-shi, Nagano, Japan
Background: Follow-up testing after the treatment of breast cancer
is not routinely recommended, as it does not have an impact on
the patients’ survival. Now that it is seriously related to their liferelated planning to know the fact of recurrence earlier, however, their
preference to strategies should be respected. Here, the ratio of several
tests performed by their own decision is investigated.
Patients and Methods: Breast cancer patients were informed in the
written form of the aim of follow-up testing, which was not to improve
survival but know distant metastases earlier from January 2012. Then
physicians advised them to select tests of their own accord. Two
hundred fifty-eight patients who had breast surgery from January 2012
to June 2014 were investigated. They were asked of their own free will
to have chest X-ray, laboratory tests at an interval of half a year, and
abdominal US and bone scanning at an interval of one year.
Results: The ratios of patients who had examinations is 67.0% for chest
X-ray, 84.9% for laboratory tests, 43.4% for abdominal US, and 26.5% for
bone scanning. Six patients were relapsed. Recurrence was found by
themselves for two patients. Three patients had no symptoms and the
follow-up tests revealed recurrence.
Discussion: Three out of six recurrent patients had no symptoms.
Therefore, there is no doubt that follow-up testing can reveal recurrence
earlier. I think it is important to have an insight into whether knowing
recurrences earlier is meaningful or not for individual patients and
into whether they want to know results earlier or not. The reason for a
wide range of test performance ratios is thought to be patients’ attitude
toward time and cost consumed for each test. More patients may select
chest X-ray and laboratory tests for this reason. Patients’ preference
must be respected and efficacy, harms and medical economy must also
be taken into account with regard to follow-up strategy.
Conclusion: When follow-up testing was to be chosen by patients
of their own accord, they were more likely to choose low-cost tests.
Follow-up strategy must be taken into account from viewpoints other
than survival.
PR124
RUMINATION AND CANCER DISEASE: A CROSS-SECTIONAL STUDY IN
A COHORT OF PATIENTS WITH BREAST AND LUNG CANCER
Silvia Riva2,1, Alessandra Gorini2,1, Mark Cropley3, Gabriella Pravettoni1,2
1
European Institute of Oncology, Applied Research Unit for Cognitive and
Psychological Science, Milan, Italy; 2Università degli Studi di Milano,
Dipartimento di Scienze della Salute, Milan, Italy; 3University of Surrey,
School of Psychology, Guilford, United Kingdom
Background: The emotional response to a breast cancer (BC) diagnosis
has been extensively studied in terms of psychological sequelae of
these events and their impact on patient’s Health-related Quality of Life
(HRQL). However, the psychological process of rumination has not been
fully studied in BC literature. Rumination is the compulsively focused
attention on the symptoms of one’s distress, and on its possible causes
and it is often associated to a traumatic experience. The diagnosis of BC
often results in rumination processes, such as appraisals of harm/loss,
intrusive beliefs and automatic thoughts.
Aim: Firstly, we aimed at evaluating the presence of ruminating in
patients who faced the traumatic experience of a diagnosis of a BC.
Secondly, we aimed at comparing rumination in BC patients VS lung
cancer (LC) patients. Thirdly, we investigated which psycho-social
variables could affect rumination among perception of the disease,
coping strategies, social support and quality of sleep.
Results: Ninety-eight (14 M, 84 F) of 100 patients (Mean age=56, SD:
10,72; 33–84 years) completed the questionnaires. Sixty-six patients
(67.3%) had a breast cancer while 29 (29.6%) were diagnosed with a
lung cancer. Rumination related with cancer, was observed in 50.3%
of patients with BC and in 46.1% patients with LC. Even no significant
statistical difference occurred between the two groups, BC patients have,
in mean, more rumination than LC patients. Rumination was highly
negatively correlated with the quality of sleep (r=0.369, p=0.000) and
positively correlated with the perception of an individual responsibility
(causes) in having a cancer (r=0.232, p=0.027).
Discussion: Rumination is a key consideration in psychological
responses of women diagnosed with BC and it is significantly associated
with the representation of the disease’s causes and quality of sleep.
These findings may inform development of therapeutic intervention
programs aimed at decreasing cancer patients’ rumination levels, which
may be correlated with higher HRQL and better adjustment. The present
study, which examined patients who have just been diagnosed with a
cancer, may enrich existing studies on the effect of a first diagnosis and
emotional outcomes.
PR125
SOME PATTERNS OF BREAST CANCER EPIDEMIOLOGY
Nanuli Ninashvili2, Mikheil Shavdia1,3
1
Palliative Care Clinic, Cancer Prevention Center, Tbilisi, Georgia; 2State
Medical University, Public Health Department, Tbilisi, Georgia; 3Tbilisi
State Medical University, Oncology Department, Tbilisi, Georgia
Background: Breast cancer is one of the serious public health concerns
in the country. It presented an interest to study epidemiology of breast
cancer to make appropriate changes in control and preventive measures.
Material and Methods: Descriptive epidemiological study was
conducted on the basis of the population-based cancer registry for over
the past decade period. Of 35 899 subjects with breast cancer 3 500
were selected by randomly. Statistical methods were applied to the
results for significance.
Results: Breast cancer ranked first in the mortality structure of female
population. The most vulnerable ages were 30-44 and 50-54. After the
age of 65 risk of breast cancer was decreasing. It was the lowest in the
age group of 70-80. Annual disease specific mortality rate constituted
48 per 100000 female population. Almost every third case of breast
cancer was detected at advanced (IV- incurable) stage. 93% of breast
cancer cases were diagnosed in secondary health care services. The vast
majority of advanced breast cancer cases were from rural areas of the
country.
Conclusions: 1. Breast cancer is a leading cause of mortality in female
population. It is likely to be the primary cause of early female mortality.
2. The vast majority of the cases are detected at advanced incurable
stage.
Recommendation: Although breast cancer screening program is in
practice in the capital and the big cities of the country, it should be
extended and expanded throughout the country.
Abstracts / The Breast 24 S3 (2015) S21–S75
PR126
ACCESS TO CARE FOR ADVANCED BREAST CANCER IN
MIDDLE-INCOME COUNTRY: EXAMPLE OF MOROCCO
Narjiss Berrada, Mrabti Hind, Mamouche Fouzia, Ettahri Hamza,
Layachi Mohammed, Raiss Hanane, Elomrani Fadoua, Ouzine Imane,
Elghissassi Ibrahim, Boutayeb Saber, Errihani Hassan
National Institute of Oncology, Medical Oncology Dpt., Rabat, Morocco
Background: Breast cancer is a real public health problem in middleincome countries. Its incidence is increasing in developing countries.
Disease is often diagnosed at late stage due to a lack of early detection
and access to treatment. Survival is worse. In addition, these countries
had limit resource to face to this expensive and complex long term
disease as well as their public health care is not adapted to the needs
generated by this escalating disease. Also, there is a different cultural,
religious and social perception of the disease. So access to care needs to
be adapted to each region. The purpose of this work was to describe the
current situation in the management of advanced breast cancer and to
identify the main challenges in Morocco.
Materials and Methods: We first realized a review of data available
in pubmed or presented in local meeting then we realized a survey
among 25 medical oncologists working in different centers about their
practices.
Results: According to Registries, advanced stage represent 7 to 14%
at first diagnosis and median age is 42 years old. Metastatic breast
cancers represent approximately 1400 case per years. 50% of patient are
premenopausal. The management of these tumors is done by different
actors both in the private and public sectors. There are 12 private clinic,
8 of them are localized in Rabat or Casablanca. Concerning public system
there are 2 department of medical oncology in teaching hospitals
(Fes and Oujda), the National Institute of Oncology is depending of
the University Hospital of Rabat. There are only 3 functional regional
center. The Princess Lalla Salma Foundation- Prevention and treatment
of cancer- is currently building new centers. Interdisciplinary team
meetings are available in 83% of centers. 33.5% of patients have
insurance, the others have gouvernement insurance or must pay for
them self. The Princess Foundation made important drug donations for
the public hospital. Chemotherapies are available in all the hospital.
New endocrine therapy and target therapy are available only in few
centers. The estimation of the cost of treatment (without pertuzumab,
TDM1, fulvestrant and everolimus) is 35.058 Euro per patient at public
hospital. No data are available from patient treated at private clinics.
75% of oncologists adhere to international guidelines (55% to NCCN
guidelines, 37% to ABC consensus). 35% of oncologits remain informed
by internet.
Conclusion: The management of advanced breast cancer in Morocco
has evolved in recent years. The main challenge in the future will be the
continuous formation of oncologists and the availability of news target
therapies.
PR127
CHANGES OF STATISTICS OF BREAST CANCER IN UKRAINE DURING
THE PERIOD OF 2003-2013
Liliya Zrelykh
Cherkassy Regional Oncology Center, Regional Oncochemotherapy Center,
Cherkassy, Ukraine
Introduction: Breast cancer (BC) is a very big problem in the world,
especially in developing countries due to its leading positions in the
structure of the incidence and mortality among other cancers in female
population.
Materials and Methods: Analysis of data of National cancer registry of
Ukraine, regional cancer registries.
Results: Number of new BC cases in 2003 in Ukraine was 15787
(men - 134, women - 15653), in 2013 - 16704 (men - 127, women 16577). So number of BC cases in women increased on 924 cases in
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2013 in comparison with 2003. Number of deaths from BC registered
in 2003 was 7921 (men - 52, women - 7869), in 2013 - 7783 (men - 74,
women - 7709). Mortality rate decreased on 138 in total population. The
age-standardised incidence rate of BC in 2013 in comparison with 2003
increased by 13,4% and age-standardised mortality rate of BC during
the period 2003-2013 increased by 0,6%. Between 2003 and 2013 the
age-standardised incidence rate of BC in women increased from 54,1 to
62,3 (by 13,16%) and age-standardised mortality rate of BC decreased
from 26,4 to 26,3 ( by 0,38%). Stage distribution of new BC cases
(according to TNM) in 2003 was: I-II - 70,8%; III - 18,4%; IV - 8,6%. In
2013 such distribution was: I-II - 77,1%; III - 13,6%; IV - 7,1%. So in 2013 in
comparison with 2003 the frequency rate of I-II stages increased by 6,3%
while frequency rate of advanced breast cancer (III-IV stages) decreased
by 6,3%. Patients with BC who received special treatment in 2003 were
75,4%, in 2013 - 82,8% (increased by 7,4%). Microscopically verified BC
cases in 2003 were 85,6%, in 2013 - 92,4% (increased by 6,8%). Patients
with BC detected during the preventive examination in 2003 were
37,7%, in 2013 - 53,7% (increased by 16%).
Conclusion: The main problems of Ukrainian oncological service are
the lack of material and technical base, insufficient funding, absence
of medical insurance, ecological problems (the consequences of the
Chernobyl disaster). Although the incidence of BC cases increased
in 2013 in comparison with 2003, the mortality rate of this disease
remained almost at the same level. Patients with BC began to be
identified at earlier stages due to the implementation of screening
programs, improvement of education of women and their greater
adherence to treatment. During the period of 2003-2013 increased the
number of patients with BC detected during the preventive examination,
those with microscopically verified BC and those who received special
treatment. Despite large number of problems there is some positive
tendency in breast cancer statistics in Ukraine in 2013 compared with
2003.
Basic and Translational Research
OR128
CTL AND IGG RESPONSE TO TUMOR-ASSOCIATED ANTIGENS AS
PREDICTIVE FACTORS OF THERAPEUTIC PEPTIDE VACCINATION FOR
PATIENTS WITH METASTATIC RECURRENT BREAST CANCER
Uhi Toh2, Mina Okabe2, Nobutaka Iwakuma2, Mai Mishima2,
Shigeki Shijijo1, Akira Yamada1, Kyogo Itoh1, Yoshito Akagi2
1
Kurume University, Cancer Vaccine Center, Kurume, Japan; 2Kurume
University School of Medicine, Department of Surgery, Kurume, Japan
We have developed a novel regimen of personalized peptide vaccination
(PPV), and conducted a phase II trial of PPV for metastatic recurrent
breast cancer (mrBC) patients to investigate the feasibility of PPV for
mrBC, in which vaccine antigens are selected and administered from
a pool of 31 different peptide candidates based on the pre-existing
IgG responses specific to peptides before vaccination. In this study,
the relation of between immune response and clinical outcome was
analyzed.
Methods: 79 patients with mrBC who had metastases and had failed
standard therapy were enrolled in this study. A maximum of 4 human
leukocyte antigen (HLA)-matched peptides showing higher peptidespecific IgG responses in pre-vaccination plasma were selected from
31 pooled peptide candidates applicable for the 4 HLA-IA phenotypes
(HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were
subcutaneously administered weekly for 6 weeks and bi-weekly
thereafter. Measurement of peptide-specific cytotoxic T lymphocyte
(CTL) and IgG responses were conducted before and after vaccination.
Levels of IgG reactive to each of the 31 peptides in the pre- and postvaccination plasma were measured using LUMINEX system at every 6
vaccination. Peptide-specific CTL responses were examined by IFN-
ELISPOT.
Results: Peptide-specific immune boosting was observed in the
majority of patients, irrespective of the breast cancer subtypes. The
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Abstracts / The Breast 24 S3 (2015) S21–S75
median progression-free survival time and median overall survival time
of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/
HER2-negative patients were 12.2 and 26.5 months, and those of HER2positive patients were 4.5 and 14.9 months, respectively. Peptidespecific IgG responses after 6 or 12 vaccinations were augmented in
7/15 (46.7%) or 9/10 (90%) patients with mrTNBC. Such augmentation
was seen in 28/40 (70.0%) or 29/31 (93.5%) patients in the luminal/
HER2-negative group, and in 16/18 (88.9%) or 11/11 (100%) patients of
the HER2-positive group, respectively. Cellular immune responses to
vaccinated peptides were assessed by IFN- ELISPOT assay. Antigenspecific CTL responses were detectable in 17/66 (25.8%) patients before
vaccination. IgG boosting was a significant prognostic factor for OS
and PFS in HER2-positive patients (p = 0.001 and 0.0001, respectively)
and CTL boosting was suggested to be a potential prognostic factor for
OS but not for PFS in mrTNBC patients, (mrTNBC, p = 0.053 and 0.345
respectively).
Conclusions: PPV could be feasible for rmBC patients, and immune
responses, IgG and CTL boosting were suggested to be a potential
prognostic factor for OS and PFS in mrBC patients, particularly for
patients with HER2-positive and TNBC.
BP129
INSULIN RESISTANCE (IR) AND PROGNOSIS OF METASTATIC BREAST
CANCER (MBC) PATIENTS
Nicoletta Provinciali4, Matteo Puntoni4, Oriana Nanni6, Paolo Bruzzi5,
Andrea DeCensi4, Laura Paleari4, Andrea Freschi2, Laura Amaducci3,
Alessandra Bologna1, Lorenzo Gianni7, Andrea Rocca6, Dino Amadori6,
Alessandra Gennari4
1
Arcispedale “S. Maria Nuova” IRCCS, Medical Oncology Unit, Reggio
Emilia, Italy; 2Centro di Riferimento Oncologico, Oncologia Medica C,
Aviano, Italy; 3Degli Infermi Hospital, Oncology Unit, Faenza, Italy; 4E.O.
Ospedali Galliera, Division of Medical Oncology, Genoa, Italy; 5IRCCS
Azienda Ospedaliera Universitaria San Martino – Ist - Istituto Nazionale
Per La Ricerca Sul Cancro, Clinical Epidemiology, Genoa, Italy; 6IRCCS
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST),
Unit of Biostatistics and Clinical Trials, Meldola, Italy; 7Ospedale Infermi,
Division of Oncology, Rimini, Italy
Background: Higher insulin levels have been associated with a worse
prognosis in early BC patients. The effect of higher insulin levels on MBC
prognosis has not been explored so far. The aim of this study was to
evaluate the influence of IR on the prognosis of HER2 negative, nondiabetic, MBC patients receiving first line CT.
Methods: The relationship between IR, identified by HOMA index
>2.5 (fasting glucose [mmol/L] × insulin [mU/L]/22.5), and progression
free (PFS) or overall survival (OS) was assessed in 125 MBC patients
enrolled in a clinical trial of first line CT with non-pegylated liposomal
doxorubicin 60 mg/sqm plus cyclophosphamide 600 mg/sqm Q21 days.
PFS and OS were calculated by Kaplan-Meier estimation; multivariate.
Cox analysis was performed adjusting for age, PS, endocrine status,
metastatic site and BMI.
Results: Information on patient’s IR status at baseline was available
on 116 women. Median follow up was 17.9 months (IQR 1–49). Overall,
46.95% patients were classified as insulin resistant (HOMA >2.5), 40.51%
were overweight (BMI 25–30) and 16.37% were obese (BMI >30). Median
age was 60 years (range 36–86); PS was 0 in 74.13% of the patients.
Endocrine status was positive in 75.08% and visceral disease was
present in 65.79%. Overall, median PFS was 10 months (IQR 8.5–12.8):
Median PFS was 11.5 months (IQR 9.6–14.6) in patients with HOMA
index ≤2.5 and 8.5 months (IQR 5.7–12.4), in patients with HOMA index
>2.5; HR = 1.332 (95% CI: 1.01–3.18, p = 0.04). By multivariate analysis,
after adjustment for age, PS, endocrine status, visceral disease and BMI,
a statistically significant higher risk of disease progression was detected
in patients with HOMA Index >2.5 (HR = 2.28; 95%CI: 1.06–4.89, p =
0.035).
Conclusions: In this study IR, indicated by an HOMA Index >2.5, was
associated with a significantly worse prognosis; after adjusting for
other acknowledged prognostic factors, the IR status together with
the ER status, were the only two to maintain their adverse prognostic
effect. These data suggest that host metabolic status might influence the
prognosis of MBC treated with CT and therefore additional alternative
strategies, targeting host metabolism, should be considered in this
unfavorable subset of patients.
PO130
CLINICAL UTILITY OF THE EXPRESSION OF HER3, HER4, PTEN AND
IGF1R IN HER2-POSITIVE ADVANCED OR METASTATIC BREAST CANCER
Hiroki Ito, Takayuki Ueno, Hirotsugu Isaka, Kaisuke Miyamoto,
Shigeru Imoto
Kyorin University Hospital, Breast Surgery Department, Tokyo, Japan
Background: Overexpression of HER3, HER4, PTEN and IGF1R has been
reported in HER2-positive advanced or metastatic breast cancer. To
assess the clinical utility of these biomarkers, the relationship between
their expression and clinicopathological factors was analyzed in HER2positive advanced or metastatic breast cancer patients treated with
first-line treatment of trastuzumab and vinorelbine.
Materials and Methods: Fifteen cases registered in the phase 2 study
were examined. Tissue specimens of primary tumor were used for
immunohistochemistry with anti-HER3 (DAK-H3-IC; Dako), anti-HER4
(HFR1; Abcam), anti-PTEN (138G6; Cell Signaling), and IGF1 receptor 
antibody (3027; Cell Signaling). Staining intensity was scored as 0, 1, 2,
and 3 in cellular membrane for HER3, HER4, IGF1R and in cytoplasm
for PTEN. Score 2 or 3 was designated as overexpression and positive.
Objective response rate (ORR) was determined by RECIST ver.1.1. Time
to treatment failure (TTF) and overall survival (OS) was calculated by
Kaplan-Meier estimates. Statistical analysis was performed using JMP
software version11 (SAS institute Japan).
Results: The median follow-up was 23 months (range 9-50 months).
The median age was 56 years (range 35-67 years). ORR was 60%: CR in 1
case, PR in 8, SD in 3, and PD in 3. Overexpression of HER3, HER4, PTEN,
and IGF1R was observed in 27%, 7%, 13%, and 13% of cases, respectively.
HER3-positive cases showed a higher percentage of ER positivity than
HER3-negative cases (50% vs 18%). There were no tumor progressions in
HER3 positive tumor. HER3-positive cases showed a tendency to have a
prolonged OS compared with HER3-negative cases (two year survival
rate: 100% vs 65%). Due to a small sample size, statistical significance
was not calculated. There was no relationship between overexpression
of HER4, PTEN and IGF1R and clinical response.
Conclusion: HER3 overexpression might be a favorable predictive marker
of trastuzumab-containing regimen in HER2-positive advanced or
metastatic breast cancer. A larger study is needed to confirm our results.
PO131
HETEROGENEITY IN THE EXPRESSION OF HORMONE RECEPTORS
AND HER2 BETWEEN THE PRIMARY BREAST CANCER AND
PULMONARY METASTASIS
Masako Sato
NHO Hokkaido Cancer Center, Breast Surgery, Sapporo, Hokkaido, Japan
Introduction: We build a treatment strategy in reference to estrogen
receptor (ER), and progesterone receptor (PgR) and HER2 status for
metastatic breast cancer. However, discordance in hormone receptors
and HER2 status has been occasionally observed between primary
and metastatic tumors. Recently, re-biopsy of metastatic tumors is
recommended to determine the appropriate treatment of metastatic
breast cancer.
Patients and Methods: We identified 13 breast cancer patients with
lung metastases which histologically diagnosed by video-assisted
thoracic surgery (VATS) in postoperative follow-up between 2000 and
2011. We have investigated the discordance of hormone receptors and
HER2 status between primary and pulmonary tumors, and the influence
of treatment and prognosis.
Abstracts / The Breast 24 S3 (2015) S21–S75
Results: The median age of primary breast cancer diagnosis was
53 years (range, 32 to 67). One patient had clinical stage I disease, 6
patients were stage IIA, 5 patients were stage IIB, one patient was
stage IIIA. The median interval from primary breast cancer diagnosis to
pulmonary metastasis diagnosis was 75 months. The concordance rate
of ER status between primary and pulmonary metastatic tumors was
77.1%, PgR status was 62.0%, HER2 status was 100% and there was no
negative-to-positive change. The median survival time after pulmonary
metastasis of 3 patients who had positive-to-negative in ER status was
16 months. 7 patients of 8 patients who had ER positive in also primary
and pulmonary metastatic tumors had started endocrine therapy; the
median survival time after pulmonary metastasis of the 7 patients was
54 months. While the median survival time after pulmonary metastasis
of the patients with which PgR status accorded was 64 months, the
patients with which PgR status discorded was 46 months.
Conclusion: The patients who have positive-to-negative in ER status are
worse prognosis, and a possibility that an endocrine therapy is invalid is
considered. However, the patients who have ER positive in also primary
and pulmonary metastatic tumors can continue an endocrine therapy
for long time, and obtain a long prognosis. The biopsy of pulmonary
metastatic lesion will bring a prognosis prediction and sometimes help
the decision of treatment strategy.
PO132
APOPTOTIC ACTIVITIES OF RECOMBINANT CELL SURFACE RECEPTOR
FAS WITHIN TUMOR MICROENVIRONMENT OF BREAST CARCINOMA
Seham Abdel-Moneim Abou-Shousha1, Soheir Rizk Demian1,
Amal Sobhy El Sedafi2, Medhat M. Anwar3, Osama Mohamed Nasr1
1
Medical Research Institute University of Alexandria, Immunology
Department, Alexandria, Egypt; 2Medical Research Institute University of
Alexandria, Pathology Department, Alexandria, Egypt; 3Medical Research
Institute University of Alexandria, Experimental and Clinical Surgery
Department, Alexandria, Egypt
Fas (CD95 or APO-1) is a cell surface molecule that initiats the extrinsic
apoptotic pathway to its own bearing cell (target cell) upon ligation with
its specific receptor; Fas ligand (FasL or CD178) expressed on the killer
cell surface such as cT lymphocyte. Insufficient apoptosis due to either
lack of proapoptotic stimuli or disturbances of the apoptotic pathway
is stongly associated with the development of breast cancers. In order
to avoid killing via this way or even fight back the immune system,
tumor cells exhibit down-regulation of Fas and up -regulation of FasL
expression. Thus, we aimed in this study to evaluate the apoptotic/antiapoptotic effect of Fas on tumor cells in intact microenvironment of
breast carcinoma.
Method: Fresh tumor and tumor distant breast tissue samples
were obtained immediately after breast resection from 20 Egyptian
female patients who subjected to modified radical mastectomy for
pathologically proved breast carcinoma. Samples were cultured in
absence and presence of appropriate concentrations of Fas molecules for
24 hours. Apoptosis levels were then measured immunohistochemicaly
using caspase3 staining reaction method.
Results: Apoptosis levels in Fas-treated tissues either tumor or normal/
benign were significantly higher than those of untreated ones (P<0.001,
P<0.005 respectively). Apoptosis level in Fas treated tumor tissue
was found to be higher than that in Fas treated normal/benign ones
(P<0.001).
Conclusion: Recombinant Fas has significant selective apoptotic
activities for breast cancer cells within the tumor microenvironment
emerging it as a promising immunotherapeutic agent for breast cancer.
Funding: this work was supported by the Alexandria Research
Enhancement Program (ALEX REP), being a part of the project titled: A
new approach to breast cancer immunotherapy: Induction of immune
mediated tumor cell apoptosis and anti-angiogenesis, Grant number:
HLTH-09 (Prof. Seham A. Abou Shousha, PI). The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
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PO133
DIFFERENTIAL EXPRESSION OF PLASMA MEMBRANE PROTEINS IN
INFLAMMATORY BREAST CANCER VIA STABLE ISOTOPE LABELED
AMINO ACIDS IN CULTURE (SILAC)
Michelle M. Martinez-Montemayor4, Ivette J. Suarez-Arroyo4,
Yismeilin Feliz-Mosquea1, Juliana Perez-Laspiur5, Rezina Arju2,
Shah Giashuddin3, Robert J. Schneider2, Luis A. Cubano4
1
Inter American University, Department of Biology, Bayamon, Puerto
Rico – USA; 2NYU School of Medicine, Department of Microbiology and
Department of Radiation Oncology, New York, USA; 3The Brooklyn Hospital
Center, Department of Pathology, Brooklyn, USA; 4Universidad Central del
Caribe School of Medicine, Department of Biochemistry, Bayamon, Puerto
Rico – USA; 5University of Puerto Rico-Medical Sciences Campus, RCMI
Translational Proteomics Center, San Juan, Puerto Rico - USA
Inflammatory breast cancer (IBC) is the most lethal and rare form of
breast cancer with a survival rate of <5% in 5y. IBC’s clinical presentation
is associated with tumor emboli, which are non-adherent cell clusters
that invade the dermal lymphatics overlying the breast, causing an
inflammatory phenotype. IBC cell lines and tumors overexpress plasma
membrane proteins such as E-cadherin and epidermal growth factor
receptor (EGFR), which are associated with maintaining tumor emboli
integrity, increased tumor growth, and metastasis. Additionally, more
than 50% of cancer drugs target membrane proteins due to their role
in cell-to-cell interaction and signal transduction, which is vital for
tumor progression in IBC. This led us to hypothesize that there might
be a differentially expressed plasma membrane proteome in IBC cells.
Herein, we characterized the IBC cell membrane proteome by culturing
non-cancerous mammary epithelial (MCF10A) and IBC cells (SUM149)
with light or heavy stable isotopes of amino acids (SILAC), respectively.
We identified and quantified the expression of 640 proteins by liquid
chromatography tandem mass spectrometry. 448 proteins displayed an
expression change ≥ 2.5-fold of which 447 were up-regulated and 1 was
down-regulated in IBC cells. Validation of 9 of the up-regulated proteins
[Metadherin (MTDH), Complement Component 1 Q Subcomponent
Binding Protein (C1QBP), Melanoma Cell Adhesion Molecule (MCAM),
Flotilin-1, Integrin Beta 5 (ITG5), L1 Cell Adhesion Molecule (L1CAM),
Macrophage Stimulating 1 Receptor (C-Met-Related Tyrosine Kinase)
(RON), Plasminogen Receptor C-terminal Lysine Transmembrane
Protein (PLGRKT), Secretory Carrier Membrane Protein 3 (SCAMP3)]
was achieved via immunoblotting in IBC cell lines. Also IHC in IBC, IDC
or non-cancerous breast tissue was performed to detect expression
and localization of 7 proteins. We confirmed increased expression of
ITG5 and MCAM in KPL-4 and SUM149 IBC cells. Moreover, 14% of
IBC tissues show SCAMP3 membrane expression, an effect not seen in
IDC or non-cancerous tissue. Both MCAM and L1CAM show differential
expression in tumor tissue, while MTDH and RON display localization
changes depending on tumor type. Future analyses include correlations
with patient survival, age at diagnosis, TNM stage, recurrence, and
metastasis. This study provides insight into the specialized IBC
membrane proteome with the potential to identify novel therapeutic
targets for this intractable disease. This project was sponsored by
NIH/NCI #1F31CA174307 to ISA, Title V PPOHA US Department of
Education #P031M105050 to UCC, NIH/RCMI #5G12RR003035 and
#8G12MD007583 to UCC, NIH/RCMI Translational Proteomics Center
#8G12MD007600 to UPR-MSC, NIH/INBRE #5P20RR016470 to UPR/UCC
and NIH/NIGMS #1SC3GM111171 to MMM.
PO134
ANALYSIS OF PRIMARY BREAST CANCER (BC) EXPRESSION OF
PROGRAMMED CELL DEATH 1 (PD-1) RECEPTOR AND PROGRAMMED
DEATH LIGAND 1 (PD-L1) TO DETERMINE ASSOCIATIONS WITH
CLINICAL CHARACTERISTICS AND OUTCOMES
Neelima Vidula3, Christina Yau1, Andrei Goga2, Hope S. Rugo2,3
1
Buck Institute for Age Research, Buck Institute for Age Research,
California, USA; 2University of California, San Francisco, Helen Diller
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Abstracts / The Breast 24 S3 (2015) S21–S75
Family Comprehensive Cancer Center, San Francisco, CA, USA; 3University
of California, San Francisco, Hematology/Oncology Department, San
Francisco, CA, USA
Background: Antitumor immunity may be dampened by the interaction
of the PD-1 receptor on tumor infiltrating lymphocytes and PD-L1
on tumor cells. Two recent phase I trials have suggested efficacy of
anti-PD-1/PD-L1 antibodies in triple negative (TN) BC. In this study,
we investigated associations between primary BC PD-1 and PD-L1
expression, clinical characteristics, and patient outcomes in publically
available databases.
Methods: We evaluated PD-1 and PD-L1 expression using microarray
data from the neoadjuvant I-SPY 1 study (n = 149). Associations with
clinical features and chemotherapy response were assessed by KruskalWallis and Wilcoxon rank sum tests, respectively. Recurrence free
survival (RFS) associations were assessed by the Cox proportional
hazard model. Pearson correlations between PD-1 and expression of
PD-L1, HAVCR2, STAT5A, FOXP3, MYC, PGR, and ESR1 were determined
in I-SPY 1 and 2 other datasets: METABRIC (n = 1992) and TCGA (n = 817).
Results: In I-SPY 1, PD-1 expression was significantly higher in HER2+
and TNBC (p = 0.003), and in grade 2/3 tumors (p = 0.043); this
association was also seen in METABRIC. PD-1 expression was associated
with pathologic complete response (p = 0.006), but this correlation did
not remain significant on subtype correction. PD-1 was not associated
with tumor stage, nodal status, lymphovascular invasion or RFS. While
PD-L1 did not correlate with tumor features, patients with PD-L1
expression in the lowest quintile had worse RFS, even after subtype
adjustment (HR 2.33, p = 0.01). In all 3 datasets, PD-1 significantly
correlated with PD-L1, HAVCR2, and STAT5A, and inversely with ESR1. In
TCGA and METABRIC, a significant inverse correlation of PD-1 with PGR
was noted. In the TN subset of TCGA and METABRIC, PD-1 significantly
correlated with PD-L1, HAVCR2, and STAT5A. In TCGA and METABRIC,
PD-L1 significantly correlated with HAVCR2 and STAT5A, and this was
also seen in the TN subset. In TCGA alone, PD-1 and PD-L1 significantly
correlated with FOXP3, and PD-1 with MYC.
Conclusions: PD-1 expression is higher in TN and other aggressive BC
subtypes. PD-1 and PD-L1 correlate with immune related genes HAVCR2
and STAT5A. Low PD-L1 expression may be an adverse prognostic factor.
Trials are underway to investigate the activity of anti-PD-1/PD-L1
antibodies in TNBC and to elucidate markers of response.
PO135
AT A GLANCE THE BRCAS EPIGENETIC STUDY IN PADANG, WEST
SUMATERA, INDONESIA
Wirsma Arif Harahap1, Dessy Arisanty2,Daan Khambri1,Yanwirasti3,
Sofia Mubarikha4
1
Medical Faculty Andalas University/Dr. M. Djamil Hospital, Department
of Surgery, Padang West Sumatera, Indonesia; 2Andalas University, Dept of
Biochemistry, Padang West Sumatera, Indonesia; 3Medical Faculty Andalas
University, Dept. of Biomedical Science, Padang West Sumatera, Indonesia;
4
Faculty of Medicine GMU, Molecular Biology Laboratory, Yogyakarta,
Indonesia
Background: Sporadic breast carcinoma is the most common cancer
among premenopausal women in Padang. There are differences of risk
factors and tumor characteristics compared with Caucasian patients
such as young age, lactation, multiparity etc. It was assumed that
promoter methylationin BRCA1 plays a role in this differences.
Materials and Methods: This study is a descriptive analytic study
aimed to describe the incidence of promoter methylation in the BRCA1
gene in sporadic premenopausal breast cancer patients in Padang. This
research used methylation with bisulfate PCR technique method in the
BRCA1 promoter in 60 sporadic premenopausal breast cancer patients
at M Djamil Hospital Padang. Stage, tumor grading, mitotic index and
immunohistochemical examination (Er, Pr, HER2, Ki67) are examined
prognostic factor. Data are analyzed using Chi-Square test.
Results: 60 breast cancer patients, 23.3% are stage II, 66.7% are stage
III and 10% are stage IV. Cancer subtypes were luminal A in 12 patients
(20%), luminal B in 16 patients (26.7%), HER2 in 10 patients (16.7%)
and TNBC in 22 patients (36.7%). Methylation in cancer tissue was
found in 39 patients (65%) where 32 patients with advanced stage
(82.1%). The result of Chi-Square test found a significant association
between methylation of stage (p=0.000) and Ki67 (p=0.000). There was
no significant association between methylation of ER (p=0.454), PR
(p=0.082), HER-2 (p=2.359).
Conclusion: Most patients came for treatment at advanced stage. The
frequency of methylation in the promoter gene BRCA1 in sporadic
premenopausal by 65% greater than literature reports. Methylation
associated with a high degree of proliferation (Ki67>14%) and advanced
stage. Breast cancer with promoter methylation in the BRCA1 gene
have a worse prognosis. Further research is needed to study the clinical
impact of antimethylation in patients with breast cancer with BRCA1
promoter methylation.
PR136
PREDICTIVE VALUE OF MRNA EXPRESSION OF TUBIII GENE IN THE
TREATMENT OF LOCALLY ADVANCED BREAST CANCER
Tatiana Semiglazova2, Petr Krivorotko3, Ekaterina Busko4,
Sergey Novikov4, Veronika Klimenko2, Elena Turkevich5, Anna Belyaeva6,
Vladislav Semiglazov1, Evgeniy Imyanitov7, Vladimir Semiglazov3
1
1st Saint-Petersburg State Medical University named after I.P. Pavlov,
Oncology, St. Petersburg, Russian Federation; 2N.N. Petrov Research
Institute of Oncology, Innovative therapy, St. Petersburg, Russian
Federation; 3N.N. Petrov Research Institute of Oncology, Breast cancer,
St. Petersburg, Russian Federation; 4N.N. Petrov Research Institute of
Oncology, Radiology diagnostics, St. Petersburg, Russian Federation; 5N.N.
Petrov Research Institute of Oncology, Pathology, St. Petersburg, Russian
Federation; 6N.N. Petrov Research Institute of Oncology, Abdominal
oncology, St. Petersburg, Russian Federation; 7N.N. Petrov Research
Institute of Oncology, Molecular oncology, St. Petersburg, Russian
Federation
Background: The most effective drugs in breast cancer treatment are
taxanes and anthracycline antibiotics. Knowledge of molecular genetics
predictive characteristics of the tumor can help not only in the choice of
cytostatic agent, but also to avoid the risk of side effects from obviously
ineffective therapy.
Methods: Patients with locally advanced breast cancer received by
randomization in neoadjuvant taxane-based regimens TAC (“docetaxel
75 mg/m2 + doxorubicin 50 mg/m2 + cyclophosphamide 500 mg/m2”)
or TC (“docetaxel 75 mg/m2 and cyclophosphamide 500 mg/m2”).
Predictive value of the expression of mRNA of the gene -tubulin class
III (TUBIII), as a marker of tumor sensitivity to taxanes, was examined
in 140 patients with locally advanced breast cancer. Depending on the
expression of TUBIII tumors patients were formed in two subgroups:
with low - 61 (43.6%) and high expression - 52 (49.5%). Detection of
mRNA expression of the gene TUBIII was carried by semiquantitative
polymerase chain reaction (PCR) in real time using a TaqMan-probes.
Pathologic response of the tumor and the lymph nodes on taxanecontaining neoadjuvant chemotherapy was evaluated by a scale MillerPayne.
Results: Pathologic complete response (pCR) in patients with low
expression TUBIII (n = 61) was registered in 19 patients (24.1%; 95%
CI: 15,2-34,2), and in the high expression group TUBIII pCR was not
registered (p <0.005). A similar correlation between low expression
of TUBIII and efficacy obtained by the intergroup analysis of TAC/TC
groups. The sensitivity, specificity, overall accuracy, and predictive value
of positive and negative results of TUBIII low expression were 94.7%,
50.4%, 56.4%, 23.1% and 98.4%, respectively. At the same time in patients
with low expression of the gene TUBIII in tumor before chemotherapy
it was marked improvement of 2-year disease-free survival compared
with patients whose TUBIII gene expression was high (80.3% vs. 51.9%,
p<0.05).
Conclusions: Thus, according to the study, low mRNA expression of the
gene -tubulin class III in breast cancer tissue can be considered as an
important sign of the effectiveness of taxane-containing chemotherapy.
Abstracts / The Breast 24 S3 (2015) S21–S75
PR137
CONTRADICTORIES IN VITAMIN D SUPPLEMENTATION ON
GENE EXPRESSION OF MICRORNAS INVOLVING IN BREAST
CARCINOGENESIS
Soraiya Ebrahimpour Koujan1, Faezeh Asghari2, Ainaz Mihanfar3
1
Tehran University of Medical Sciences, Schools of Nutritional Sciences and
Dietetics, Tehran, Iran; 2Tabriz University of Medical Sciences, Faculty of
Medicine, Department of Immunology, Tabriz, Iran; 3Tabriz University of
Medical Sciences, Faculty of Medicine, Department of Biochemistry, Tabriz,
Iran
Background and Objective: MicroRNAs (miRNAs) are small noncoding
RNAs that over and down expression of them related to some human
malignancies such as breast cancer. The aim of our review study is the
surveying the contradictory effects of vitamin D supplementation on
gene expression of specific miRNAs involving in breast carcinogenesis.
Materials and Methods: This review compromised on published articles
in PubMed and GoogleScholar according to key words since 2000.
Results: Generally there are two functionally groups miRNAs in breast
cancer. One group is tumor-suppressor miRNA that regulate cell
proliferation and apoptosis. Another group is oncogenic miRNA that
mediate invasion, metastasis, angiogenesis and drug resistance. miRNA
-221, miRNA-29ab, miRNA-26a and miRNA155 upregulated in esterogen
receptor positive of breast tumors and induce epithelial-mesanchymal
transition, metastasis and tumor progression thus these oncogenic miRNA related to invasiveness properties of tumors. Versus, mi-RNA 17/92
down-regulated in lymph node positive breast tumors therefore it has
relatively tumor-suppressor properties. Based on recent clinical trial,
vitamin D supplementation up-regulates the miRNA -221, miRNA-29ab
and miRNA-26a. These adverse effects of vitamin D may be undesirable
for breast cancer patients. Whereas, it has been shown that vitamin
D supplementation down-regulates the miRNA-17/92 as a tumorsuppressor miRNA. However, it has favorable effect on miRNA-155
regultion and it can be down-regulate by vitamin D supplementation.
Conclusion: In conclusion there are major conflictions in
supplementation of breast cancer patients with vitamin D that effect
on specific miRNA gene expression in breast cancer. Thus before clinical
use of vitamin D or supplementation of breast cancer patients with
vitamin D in human clinical trials, the cellular mechanism and its effects
should be investigated further and clarified.
S69
nodes is almost not taken into account to clinical decisions, mainly
due to the assumption that their positivity would be the same that
the one scored at the primary tumour. In fact, there is a lack of specific
axillary biomarkers to predict patient prognosis when the N is positive.
Based on the cancer stem cell (CSC) concept, we hypothesised that CSC
markers could be good candidates to be tested as biomarkers in axillary
metastases, in order to evaluate, at diagnosis, how patient’s prognosis
will be. For that, we studied the expression of P-cadherin, CD44 and
CD49f, already associated to stem cell properties in breast cancer, in a
series of 135 primary tumours and synchronous axillary lymph node
metastases. We found that P-cadherin expression in lymph node
metastases was significantly associated with poor patient’s overall
and disease-free survival. Moreover, although the majority of the cases
have shown a concordant result between the primary tumour and the
lymph node, we found some discrepancies. P-cadherin and CD49f were
enriched in the lymph nodes when the matched primary tumours
were negative, being this gain mainly found within the triple negative
molecular subtype. Importantly, we still found that cases that gained
P-cadherin expression in lymph node metastasis presented the worst
disease-free and overall survival of the whole series, as well as the ones
that lost its expression in the lymph nodes, showed a good prognosis
besides the positive expression at the primary tumour. In conclusion,
P-cadherin is an important predictor of disease outcome of breast
carcinomas with lymph node involvement, being a valuable marker for
disease progression surrogate end points. These results should be put in
perspective, together with the ones obtained by the ACOSOG Z0011 and
IBCSG 23-01 studies, where we can understand that the term “positive
axilla” is actually very deceptive. In both trials, patients with positive
sentinel lymph nodes showed the same results considering surrogate
points as overall survival, independently of being subjected to axillary
lymph node dissection.
PO139
RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA B (RANK)
EXPRESSION IN PRIMARY BREAST CANCER CORRELATES WITH
RECURRENCE FREE SURVIVAL AND DEVELOPMENT OF BONE
METASTASES IN THE I-SPY 1 TRIAL (CALGB 150007/150012; ACRIN
6657)
Neelima Vidula3, Christina Yau1, Jiali Li4, Hope S. Rugo2,3
Buck Institute for Age Research, Buck Institute for Age Research, CA, USA;
2
University of California, San Francisco, Helen Diller Family Comprehensive
Cancer Center, San Francisco, CA, USA; 3University of California, San
Francisco, Hematology/Oncology Department, San Francisco, CA, USA;
4
Valley Medical Oncology Consultants, Oncology, CA, USA
1
PO138
P-CADHERIN: A CANDIDATE BIOMARKER FOR AXILLARY-BASED
BREAST CANCER DECISIONS IN CLINICAL PRACTICE
Maria Rita Dionisio4,6, Andre Filipe Vieira6, Madalena Gomes6,
Jorge Cameselle-Teijeiro2, Manuela Lacerda5, Isabel Amendoeira1,
Fernando Schmitt7, Joana Paredes6,3
1
Centro Centro Hospitalar de São João, Department of Pathology and
Oncology, Porto, Portugal; 2Complexo Hospitalar Universitario de Vigo
CHUVI, Department of Pathology, Vigo, Spain; 3Faculty of Medicine of the
University of Porto, Department of Oncology, Porto, Portugal; 4Hospital
de Santa Maria CHLN Lisboa, Dept. of Medical Oncology, Lisbon, Portugal;
5
Instituto Português de Oncologia Coimbra, Department of Pathology,
Coimbra, Portugal; 6IPATIMUP and Instituto de Investigação e Inovação em
Saúde, Cancer Genetics, Porto, Portugal; 7Laboratoire National de Santé,
Department of Pathology and Medicine, Dudelange, Luxembourg
Breast cancer is the most frequent cancer in women worldwide and
a major cause of morbidity and mortality. Metastatic spread is the
major reason behind the fatal outcome: 6-10% of the patients present
metastatic disease at diagnosis and systemic recurrence develops
in 25-30% of patients treated with curative intent. According to the
Guidelines of ESMO2013, the presence of axillary lymph node (N)
metastases is one of the most important prognostic factors in breast
cancer and a cornerstone to clinical practice decisions. However, the
molecular biology related with the cancer cells growing in the lymph
Background: The receptor activator of nuclear factor kappa B (RANK)/
RANK ligand (RANKL)/Osteoprotegerin (OPG) axis may be involved in
the development of bone metastases. We studied gene expression in this
pathway in primary breast cancer (BC) to determine correlations with
clinical characteristics and outcomes in the neoadjuvant I-SPY 1 study.
Methods: We evaluated RANK/RANKL/OPG expression with gene
microarray studies in I-SPY 1 (n=149), using GSE25066 (n=425) for
validation. Associations with clinical features were determined with
the t-test and ANOVA. An optimal biomarker cut point to dichotomize
recurrence free survival (RFS) curves was determined using I-SPY 1,
and then the association between dichotomized biomarkers and RFS
was evaluated with the multivariate Cox proportional hazard model.
Associations with site specific relapse were determined with the
t-test and multivariate logistic regression. Pearson correlations with
a significance threshold of p <0.05 with a filter to identify genes with
similar concordance in both datasets were used to identify external
genes associated with RANK.
Results: In I-SPY 1, at 3.5 years, 41 patients developed recurrent
disease. 12 patients had any bone metastases (BM) and 22 had non bone
metastases (NBM). RANK was significantly higher in hormone receptor
(HR) negative vs. HR positive (p=0.027), basal vs. non basal (p=0.004),
and pathologic complete response (p=0.038) tumors; the associations
with HR negative and basal BC were also significant in GSE25066. In both
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Abstracts / The Breast 24 S3 (2015) S21–S75
datasets, higher RANK associated with significantly worse RFS (I-SPY
1: p=0.045, GSE25066: p=0.044). In I-SPY 1, higher RANK expression
significantly correlated with BM vs. NBM (p=0.045), even on HR status
adjustment (p=0.035). 9 external genes had positive concordance with
RANK in both datasets.
Conclusion: RANK is higher in HR negative and basal BC, and correlates
with worse RFS and BM. Targeting this pathway may improve outcomes.
PO140
CHANGING IN TUMOR BIOLOGY OF TRIPLE NEGATIVE BREAST
CANCER BETWEEN PRIMARY AND METASTATIC LESIONS
Marijana Milovic-Kovacevic, Snezana Susnjar, Ljiljana Stamatovic
Institute for Oncology and Radiology of Serbia, Department of Medical
Oncology, Belgrade, Serbia
Triple-negative breast cancer (TNBC) is defined by a lack of expression
of both estrogen and progesterone receptor as well as human epidermal
growth factor receptor 2. A recent analysis indicates that TNBC carries a
distinct molecular profile when compared with HR-positive BC. Scientific
efforts have aimed for an identification of (immunohistochemical)
markers in conjunction with TNBC status hypothesizing that TNBC is a
heterogeneous entity with basal-like breast cancer (BLBC) representing
only one presumable subtype. For breast cancer patients whose disease
has metastasized, tumor biology sometimes changes between primary
and metastatic lesions. Between May 2005 and Feb2012, 416 breast
cancer patients with initially TNBC aged 26 to 84 (57 ± 2) years were
evaluated who had oncological therapy in clinic of oncology Institute of
Oncology and Radiology of Serbia. Thirty three (7.93 %) out of 416 patients
developed local recurrence and in 9 (27.3%) of them the local recurrence
was the first site of metastasis. Histological sub-types of this BC include:
Infiltrating ductal carcinoma 20 (60.6 %), infiltrating lobular carcinoma 9
(27.3%), ductulo-lobular type 2 (6.1 %), and medular carcinoma 2 (6.1%).
There were 10 pts out of 33 with initially pure triple negative histology
defined as ER/PgR (both score 0) and HER2 negative (IHC 0). Nineteen
of the 33 patients had relapsed disease manifested with only local
recurrence, while fourteen patients developed disseminated metastases
other than local recurrence. In all 33 patients we performed a biopsy of
local recurrence allowing histological type of local recurrence, which
we compared with the initial histology of the primary tumor. In 18 of
33 pts we analysed expression in immunohistohemical status of steroid
hormone receptors (HR) such as estrogen receptor (ER) and progesterone
receptor (PgR) in concert with the oncogene ErbB-2/human epidermal
growth factor receptor 2 (HER-2). There was no change in histological
subtype between primary tumor and local recurrence. However there
was just one important change in SR status between primary tumor (ER
scor 0, PGR scor 0 and Her2 1+) and local recurrence (ER sc 8, PgR sc
7, Her 2 0) and two unimportant: primary tumor (ER scor 0, PGR scor
0 and Her2 0) and local recurrence (ER sc 0, PgR sc 2, Her 2 1+). Our
results shows that there was not identified any significant statistical
change in tumor biology between primary tumor and metastatic lesion.
Consistent with previous studies, our results confirm that there are
no any significant change in tumor biology and immunohistohremical
expression of ER or Pgr receptor, HER 2 or gene amplification of Her 2
during the natural history of the disease of TNBC.
PO141
SUCCESSFUL USE OF HER2 TARGETED AGENTS IN PATIENTS WITH
HEAVILY PRETREATED HER2-NEGATIVE METASTATIC BREAST
CANCER PRESENTING WITH ELEVATED SERUM LEVELS OF THE
HER2 EXTRACELLULAR DOMAIN AND/OR HER2 OVEREXPRESSING
CIRCULATING TUMOR CELLS
Christian Martin Kurbacher1, Annegret Quade1, Gerhard Kunstmann3,
Susanne Herz1, Jutta Anna Kurbacher2, Matthias R. Warm4
1
Gynecologic Center Bonn-Friedensplatz, Gynecologic Oncology Dpt., Bonn,
Germany; 2Gynecologic Center Bonn-Friedensplatz, General Gynecology
and Obstetrics, Bonn, Germany; 3Krankenhaus Köln-Holweide, Internal
Medicine (Hematology/Oncology), Cologne, Germany; 4Krankenhaus KölnHolweide, Senology, Cologne, Germany
Background: A considerable proportion of patients (pts) with HER2negative (HER2-) metastatic breast cancer (MBC) present with elevated
serum levels of the HER2 extracellular domain (sHER2) and/or HER2
overexpressing circulating tumor cells (CTCs) during their further
clinical course. These “occult” HER2-positive (HER2+) pts may be
candidates for anti-HER2 therapy (Tx) albeit normally not subjected to
such treatment. This observational study was undertaken to gain more
insights into the feasibility of HER2-directed Tx in pts with tissue HER2MBC with elevated sHER2 levels and/or HER2+ CTCs in the clinical
routine.
Methods: A total of 28 pts with heavily pretreated HER2- MBC (ER+,
n=24) showing sHER2 values > 15 ng/mL (n=8), HER2+ CTCs (n=6), or
both (n=14) were included. sHER2 was determined by a commercial
chemiluminescence immunoassay (Siemens Healthcare Diagnostics,
Eschborn, Germany), CTCs were detected by using the CellSearch(TM)
technology (Veridex, Raritan, NJ). Pts had failed 2-16 prior systemic
treatments (median: 7). All pts received anti-HER2 Tx with trastuzumab
(H: n=16), lapatinib (L: n=4), H+L (n=2), or H+pertuzumab (H+P: n=6).
HER2-targeting Tx was given alone (n=4), or in combination with
endocrine agents (n=5), cytotoxics (n=16), or other targeted drugs (n=3).
Responses were scored according to RECIST 1.1, OS was calculated from
the start of HER2-directed Ctx until death from any reason or loss to
follow-up by using Kaplan-Meier statistics.
Results: Anti-HER2 Tx was generally well tolerated. Median treatment
duration was 17.0 wks (range 1.0-56.1 wks). In 2 pts with L and 1 pt
with H+L, Tx was prematurely stopped due to inacceptable toxicity
(diarrhea, fatigue). Whereas 5 pts progressed on Tx, 11 pts achieved PR
and another 12 pts experienced SD accounting for an objective response
rate (ORR) of 39.3% and a clinical benefit rate (CBR) of 82.1%. Median OS
was 76.1 wks. All pts with PR or SD showed declining CTC counts within
6 wks from start of Tx whereas sHER2 decreased only in pts responding
on L-free regimens.
Conclusion: Our findings indicate that anti-HER2 Tx may be a valid
option in pts with heavily pretreated HER2- MBC with pathological
sHER2 values and/or HER2+ CTCs in the clinical routine. Serial CTC counts
may be the more appropriate predictor of clinical benefit as compared
to sHER2. It is unclear at present whether pts included in this study
have really shifted from HER2- to HER2+ during their clinical course or
should more likely be regarded as false HER2- individuals due to wellknown limitations of the preceding HER2 analyses in tumor tissue. Thus,
results of ongoing randomized trials in this setting are eagerly awaited.
PO142
EVOLUTION OF THE EXPRESSION OF CIRCULATING TUMOR CELLS
(CTC) AND CK-19 MRNA (CK19) AS PROGNOSTIC FACTORS IN HEAVILY
PRETREATED METASTATIC BREAST CANCER
Serafín Morales Murillo, Ana Velasco Sánchez, Ariadna Gasol Cudos,
Juan Felipe Córdoba Ortega, Jose Vidal, Anna Serrate López,
Joan Valls, Juan Carlos Samame Pérez-Vargas, Ramon Gisbert,
Desamparados Moral, Antonio Llombar Cussac, Antonieta Salud Salvia,
Xavier Matias-Guiu Guia
Hospital Universitari Arnau de Vilanova de Lleida, Department of Medical
Oncology, Lleida, Spain
Introduction: The expression of CTC and CK19 has prognostic value for
patients with metastatic breast cancer but their clinical significance
remains still controversial. We have found a relation between high CTC
and CK19 expression in peripheral blood samples with bad prognosis,
but if these values are maintained just after starting a new treatment
could determine early resistance it´s unknown.
Methods: This clinical observational study included 67 preteated
metastatic breast cancer patients who started a standard new treatment
line. CTC and CK19 were measured with CellSearch® and RT-PCR
respectively at inclusion time and after their first cycle of the new
Abstracts / The Breast 24 S3 (2015) S21–S75
line of treatment. Progression-free survival (PFS) was defined as the
time between the initiation of the treatment and either the date of
clinical or radiological progression or death or the last follow-up. Cox
proportional hazards regression model was used to assess the univariate
prognostic value of CTC and CK19 on PFS, and Kaplan-Meier estimates. A
multivariate Cox model was also performed to additionally account for
ER and visceral disease.
Results: Mean age was 59.68 (range 35-86), the average number of
previous treatments was 2.98 (range 1-10), 42 patients (62.6%) were ER+
and 38 (56.7%) had visceral disease. Median PFS was 8 months (CI 95%
3.7-8.2). Univariate analyses showed a significant effect of initial values
of CK19 (HR=2 , CI 95% 1.05-3.8, p=0.03) and for the second value of
the CTC (HR=2.18, CI 95% 1.22-3.9, p=0.009) but did not reach statistical
significance for the initial value of CTC and the second value of CK19.
The estimate disease-free survival rate (DFS) at 6 and 12 months were
75% and 31% for patients with low values of CK19 and 36 % and 10 % for
high values (p:0.022). While the DFS rate at 6 and 12 months were 86%
and 65% for patients with low second value of the CTC and 76 % and 47%
for patients with high value (p:0.004), respectively. In the multivariate
analysis adjusted by ER and visceral disease the effect of the second
value of CTC remain significative (HR=2.7, p=0.004).
Conclusions: The expression of CK19 and CTC appeared clinically
meaningful in pretreated metastatic breast cancer patients, even when
adjusted by ER and visceral diseases. The value of the CTC immediately
after an initial treatment is a strongest predictor of survival. These
results support CK19 and CTC as an interesting biomarker for predicting
clinical response in metastatic breast cancer.
PO143
PROGNOSTIC IMPACT OF CIRCULATING TUMOR CELL CLUSTERS AND
APOPTOSIS IN METASTATIC BREAST CANCER
Sara Jansson1, Pär-Ola Bendahl1, Anna-Maria Larsson1,
Kristina Aaltonen1, Lisa Rydén2
1
Lund University, of Clinical Sciences, Division of Oncology and Pathology,
Lund, Sweden; 2Skåne University Hospital Lund, Department of Clinical
Sciences, Division of Surgery, Lund, Sweden
Circulating tumor cell (CTC) quantification in breast cancer has recently
been assessed in a large pooled analysis confirming that CTC count has
an independent prognostic value. However, it remains unknown to what
extent the malignant potential of CTCs is reflected in their morphological
characteristics. Studies have shown that presence of apoptotic CTCs and
CTC-clusters is associated with decreased progression-free survival
(PFS). The aim of this study was to morphologically characterize
CTCs in women with metastatic breast cancer, and to correlate these
characteristics to breast cancer subtype and prognosis. Women with
metastatic breast cancer have since 2011 been enrolled in a Swedish
study with the aim of enumerating and characterizing CTCs using the
CellSearch® system. Patients with ≥5 CTCs per 7.5 ml blood at baseline
(BL) were selected for this project. Sequential blood samples were drawn
at 3 and 6 months. CTCs were evaluated for apoptotic changes, clusters
(defined as a group of CTCs displaying ≥3 nuclei), and CTC-leukocyte
clusters (defined as ≥1 CTC with ≥1 leukocyte attached). 52 patients
with a median BL CTC count of 45 (range 5-668) were included in this
study. 39 patients had hormone receptor (HR) positive breast cancer, 7
had HER2-amplification and 4 had triple-negative breast cancer (TNBC).
2 patients had unknown status. 9 patients had ≥1 CTC cluster (range
1-18) present at BL. TNBC and HER2-amplified breast cancer had clusters
present at higher rate than HR positive cancer (p-value=0.01). In total, 14
patients had ≥1 CTC cluster present at any time during the study. Of the
9 patients with clusters at BL, 6 were cluster free in all subsequent blood
samples. These 6 patients had a significantly longer PFS compared to the
patients with clusters present at any follow-up blood sample (p-value
0.02). 35 patients had ≥1 CTC-leukocyte cluster at BL. No difference
was seen in PFS depending on presence of CTC-leukocyte clusters. 40
patients had ≥1 apoptotic CTC at BL and no difference in PFS was seen
compared to patients with no apoptotic CTCs present (p-value=0.3).
However the cut point to best separate patients according to apoptotic
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status of CTCs is unknown. A cut point of ≥10% apoptotic CTCs at BL
identified a group of 11 patients that had a tendency towards poorer PFS
(p-value 0.1). Detection and quantification of CTCs by the CellSearch®
system has recently reached the highest level of clinical evidence. We
have conducted an explorative study on CTC morphology in metastatic
breast cancer where we show that CTC-clusters and apoptosis in the
CellSearch® CTC gallery can provide additional prognostic information
to enumeration. Intriguingly, patients who fail to eradicate CTC-clusters
from their blood during treatment have a poor prognosis.
PO144
SYNERGISTIC ANTITUMOR EFFECTS OF CROCIN COMBINED WITH
HYPERTHERMIA ON BREAST CANCER CELLS
Reyhane Hoshyar1, Elham Mostafavinia1, Mohammad Reza Abedini2
1
Birjand University of Medical Sciences, Faculty of Medicine, Department
of Biochemistry, Birjand, Iran; 2Birjand University of Medical Sciences,
Faculty of Medicine, Department of Pharmacology, Birjand, Iran
Currently there is considerable interest among scientists to find effective
anticancer drugs in herbal components such as carotenoids of saffron
stigma. Besides hyperthermia is a promising treatment of breast cancer
that inhibited cell growth as well as improved the efficacy of chemoand radiotherapy. We investigated the anti proliferative properties of
combination of crocin with hyperthermia on human breast cancer cells
(MDA-MB-468). The cancer cells exposed with high temperature (43°C
for 2 h), then treated with different concentration of crocin (0-5 mg/ml).
Cell viability, cell colony formation ability and cell apoptosis assessed,
respectively, by MTT, soft agar, Hoechst 33258 staining and lactate
dehydrogenase (LDH) release % methods. Also, the expressions of heat
shock proteins (Hsp70 and Hsp90) mRNA determined by quantitative
real-time PCR. The combination of hyperthermia and crocin revealed
a dose- and time-dependent cytotoxic effect against MDA-Mb-468
cell line. This combination treatment significantly decreased colony
forming ability of cancer cells in soft agar with inhibition rate about 94
% compared to crocin (p < 0.001). Our data illustrated an increase in the
percentage of cells undergoing apoptosis, as measured by evaluation of
nuclear morphology by Hoechst 33258 nuclear staining. Furthermore
the percentage of LDH release that apoptosis-inducing effect of this
combination therapy was much more than crocin, alone. The treated
cells (1.5 mg/ml crocin) markedly down regulated the expression of
anti-apoptotic and heat induced genes including Hsp90 and Hsp70 (p
< 0.001). In conclusion, hyperthermia enhanced the antitumor effects
of crocin against breast cancer through reduction of the expression
of Hsp70 and Hsp90. Our study suggested that hyperthermia has
synergistic effects when combined with crocin and can be applied as a
novel therapy for human breast cancer.
PO145
ICORG 13-01 ABC SURVEY: ARE WE MEETING THE NEEDS OF
PATIENTS WITH ADVANCED BREAST CANCER (ABC) IN IRELAND?
A NATIONWIDE SURVEY
Jodie E. Battley4, Rose Beamish4, Miriam O’Connor13, Verena Murphy1,
Algirdas Stockunas1, Conleth G. Murphy3, Brian R. Bird3,
Deirdre O’Mahony4, Jeffri R M. Ismail5, Karen A. Duffy6,
Janice M. Walshe10, John P. Crowne10, Michael J. Martin8,
Catherine M. Kelly7, M. John Kennedy9, Linda Coate12, Hennessey Brian2,
Maccon Keane11, Seamus O’Reilly4
1
All Ireland Cooperative Oncology Research Group, Oncology Clinical
Research, Dublin 2, Ireland; 2Beaumont Hospital, Medical Oncology, Dublin
5, Ireland; 3Bon Secours Hospital, Medical Oncology, Cork, Ireland; 4Cork
University Hospital, Medical Oncology, Cork, Ireland; 5Kerry General
Hospital, Medical Oncology, Kerry, Ireland; 6Letterkenny General Hospital,
Medical Oncology, Donegal, Ireland; 7Mater Misericordiae University
Hospital, Medical Oncology, Dublin 7, Ireland; 8Sligo General Hospital,
Medical Oncology, Sligo, Ireland; 9St. James’s Hospital, Medical Oncology,
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Abstracts / The Breast 24 S3 (2015) S21–S75
Dublin 8, Ireland; 10St. Vincent’s University Hospital, Medical Oncology,
Dublin 4, Ireland; 11University Hospital Galway, Medical Oncology, Galway,
Ireland; 12University Hospital Limerick, Medical Oncology, Limerick,
Ireland; 13Waterford General Hospital, Medical Oncology, Waterford,
Ireland
Background: Despite a continuous decline in mortality since the early
1990s, breast cancer remains the second leading cause of cancer death
in women in Ireland. One fifth of patients who are diagnosed with
breast cancer in Ireland will develop metastatic disease. Recent studies
have emphasized the significant unaddressed needs of patients living
with metastatic breast cancer. Traditionally, resourcing for patients
with breast cancer has focused on those with newly diagnosed and
potentially curable disease. Many patients compare unfavorably the
abundant support received at diagnosis to the dearth of support present
at relapse. We hypothesise that there is a significant unmet burden of
illness in patients living with metastatic breast cancer in Ireland; the
purpose of this study is to quantify this.
Methods: A 76-item questionnaire was developed by the All-Ireland
Cooperative Oncology Research Group (ICORG) in collaboration
with metastatic breast cancer patients. This comprises a health
questionnaire, investigating perceived psychological and social needs,
activities promoting health and well-being, and access to supports. The
survey incorporates quality of life measures: The European Organisation
for Research and Treatment of Cancer Quality of Life Questionnaire
(EORTC QLQ-C15-PAL), and breast-specific systemic adverse effects
scale (EORTC BR-23). This survey was conducted from February 2013
to February 2015. Five hundred patients with metastatic breast cancer
were recruited from 8 National Cancer Control Programme (NCCP)
centres and affiliated teaching hospitals in Ireland. We propose to
present the data on this cohort.
Study objectives: The primary end point of this study is the quantification of the quality of life and support needs of patients living with
metastatic breast cancer in Ireland. The results of this study will direct
further research and inform service development in order to improve
patient outcomes.
PR146
LOCOREGIONAL RECURRENCE BY TUMOR BIOLOGY IN BREAST
CANCER PATIENTS AFTER PREOPERATIVE CHEMOTHERAPY AND
BREAST CONSERVATION TREATMENT
Eunjin Jwa2, Kyung Hwan Shin1, Ja Young Kim1, So-Youn Jung1,
Eun Sook Lee1, In Hae Park1, Keun Seok Lee1, Jungsil Ro1, Yeon-Joo Kim1,
Tae Hyun Kim1
1
Research Institute and Hospital, National Cancer Center, Center for Breast
Cancer, Goyang, Korea; 2Soon Chun Hyang University College of Medicine,
Radiation oncology, Cheonan, Korea
Purpose: To determine whether breast cancer subtype affect ipsilateral
breast tumor recurrence (IBTR) and locoregional recurrence (LRR) after
neoadjuvant chemotherapy (NAC) and breast-conserving therapy (BCT).
Methods: We evaluated 335 consecutive patients with clinical stage IIIII breast cancer who received NAC plus BCT from 2002 to 2009. Patients
were classified into six molecular subtypes: luminal A (hormone
receptor (HR)+/HER2-/Ki-67<15%, n= 113), luminal B1 (HR+/HER2-/Ki67 ≥15%, n=33), luminal B2 (HR+/HER2+, n=83), HER2 with trastuzumab
[HER2(T+)] (HR-/HER2+/use of trastuzumab, n=14), HER2 without
trastuzumab [HER2(T-)] (HR-/HER2+, n=31) and triple negative (TN)
(HR-/HER2-, n=61).
Results: After a median follow-up of 7.2 years, 26 IBTRs and 37 LRRs
occurred. The 5-year IBTR-free survival rates were 97.2, 93.9, 92.8,
92.9, 89.1, and 84.6% in luminal A, B1, B2, HER2(T+), HER2(T-), and TN
patients, respectively. The 5-year LRR-free survival rates were 96.4, 93.9,
90.3, 92.9, 78.3, and 79.6% in luminal A, B1, B2, HER2(T+), HER2(T-),
and TN patients, respectively. On multivariate analysis, HER2(T-) (IBTR,
hazard ratio=4.2, p=0.04; LRR, hazard ratio=7.6, p<0.01) and TN subtypes
(IBTR, hazard ratio=6.9, p=0.01; LRR, hazard ratio=8.1, p<0.01) were
associated with IBTR and LRR. Although a pathologic complete response
(pCR) was not associated with improved IBTR or LRR in any patients, it
was found to correlate with better LRR and a tendency toward improved
IBTR controls in TN patients (IBTR, p=0.07; LRR, p=0.03).
Conclusions: The TN and HER2(T-) subtypes predict higher rates of IBTR
and LRR after NAC and BCT. In cases of non-TN subtypes, a pCR is not
predictive of improved IBTR or LRR.
PR147
INTRATUMORAL MORPHOLOGICAL HETEROGENEITY OF BREAST
CANCER AND ITS IMPLICATION IN CHEMOTHERAPY RESISTANCE
Tatiana Gerashchenko1,3, Evgeny Denisov1,3, Marina Zavyalova2,
Nadezhda Cherdyntseva1,3, Vladimir Perelmuter2
1
Tomsk Cancer Research Institute, Molecular Oncology and Immunology,
Tomsk, Russian Federation; 2Tomsk Cancer Research Institute, Pathological
Anatomy and Cytology, Tomsk, Russian Federation; 3Tomsk State
University, Translation Cell and Molecular Biomedicine, Tomsk, Russian
Federation
Background: Intratumor heterogeneity can affect the chemotherapy
efficacy and represents a unique platform for the development of
targeted therapies. We tried to investigate the influence of intratumor
morphological heterogeneity of breast cancer (BC) on chemotherapy
response and to clarify the molecular mechanisms of associations,
obtained here.
Methods: 382 BC patients were enrolled to estimate the association
between neoadjuvant chemotherapy (NAC) efficiency and the
presence of different types of morphological structures in tumors. To
understand the molecular mechanism of association of intratumor
morphological heterogeneity with chemoresistance, we compared the
expression of drug resistance genes (ABC transporter genes, GSTP1
gene, and drug target genes) between distinct morphological structures
of breast tumors (n=4) using laser microdissection-based qPCR. To
identify possible chemoresistant markers of morphological structures,
transcriptome-wide array analysis was used (SurePrint G3 Human Gene
Expression 8x60K v2, Agilent).
Results: Patients with alveolar and trabecular structures were more
frequently NAC nonresponsive (61.9% vs. 46.4%, p=0.0028; 58.8% vs.
45.3%, p=0.0272, respectively) than cases without this structural type.
Chemoresistance, related to alveolar structures, was observed in
lymph node positive BC patients (p=0.005), but not in cases without
lymphogenic metastases. In addition, in NAC nonresponsive group,
cases with alveolar structures displayed high frequency of lymph node
metastasis in comparison with ones without this morphological variant
(71.3% vs. 30.9%, p<0.0001). Trabecular structures showed many active
ABC transporter genes compared to other morphological variants (75.0%
vs. 46.4%-60.7%, p=0.055). Moreover, ABCB1 and ABCG2 gene expression
(the key ABC transporter genes) was found only in trabecular structures.
In contrast, alveolar structures showed low activity of ABC transporter
and drug target genes. Nonetheless, transcriptome-wide array analysis
showed different genes, which were significantly up-regulated in
alveolar structures: BGN, DZIP3, NIPAL2, ANKRD54 etc.
Conclusions: Alveolar and trabecular structures show aggressive
chemoresistant potential and impede to chemotherapy response. In
case of trabecular structures it probably explained by high activity of
ABC transporter genes. The contribution of alveolar structures to drug
insensitivity can be linked with other gene pathways, which association
with chemoresistance requires to be confirmed in the future research.
Anyway, chemoresistance properties of alveolar and trabecular
structures can make them as attractive targets in the development of
precision therapy.
Research is supported by Russian Science Foundation Grant: No. 14-1500318
Abstracts / The Breast 24 S3 (2015) S21–S75
PR148
ANDROGEN RECEPTOR (AR) EXPRESSION AS A PROMISING INDEX
OF THE PREDICTION OF DISTANT METASTASIS OF TRIPLE NEGATIVE
BREAST CANCER (TNBC)
Noriko Miwa3,1, Takahito Onishi2, Seigo Nakamura3
1
Nishiwaki Municipal Hospital, Breast Surgical Oncology, Nishiwaki-city,
Japan; 2Nishiwaki Municipal Hospital, Pathology, Nishiwaki-city, Japan;
3
Showa University, Breast Surgical Oncology, Tokyo, Japan
Introduction: The gene expression profiling is useful but sometimes
inappropriate in the life-threatening disease, therefore, it is important
to handle the usual method like IHC especially for the treatment of
advanced breast cancer. We focused AR because it could subdivide
TNBC into AR-positive “modest” TNBC and AR-negative “aggressive”
TNBC. In order to clarify the biological feature of AR-negative TNBC,
the relationship among the expression of AR, the sensitivity to the
chemotherapy, and the tendency to distant metastasis was studied.
Method: Twenty four TNBCs diagnosed in our hospital from 2011
through 2014 were examined. AR expression was estimated by IHC and
shown as the percentage of positive cells (0-100%) using the specimen
at diagnosis. The histological therapeutic effect of PST and the distant
metastasis were also checked. As reference, luminal-like type and HER2enriched type were explored.
Results: 1. AR expression in TNBC was 35±45% for early tumor (n=13),
12±29% for distantly metastasized disease (n=9), and 86±15% for
locoregional recurrence and large tumor without metastasis (n=3).
2. In HER2-enriched, luminal A-like, and luminal B-like tumors AR
expression were 69±32% (n=14), 81±17% (n=8), and 73±36%(n=11)
for early tumor, and 70% (n=1), 86±15% (n=3), and 40 (±56%) (n=2)
for distantly metastasized disease, respectively 3. AR expression and
histological therapeutic effect of TNBC : 0, 0, 5, 100% for grade 3 (n=4),
0% for grade 2 (n=1), 0, 0, 5, 80, 100% for grade 1 (n=5), 0% for grade 0
(n=1). Three of the eleven cases after PST recurred by distant metastasis
within 1 year of which histological therapeutic effect was grade 1-0 and
AR was not expressed.
Discussion: 1. The triple negative and luminal B-like breast cancers
with low AR expression had tendency to the distant metastasis different
from HER2-enriched and luminal A-like tumors. The TNBC with pCR
followed good prognosis even if AR expression was low. 2. The obvious
relationship between AR expression and the histological therapeutic
effect in TNBC was not detected. 3. The AR expression decreased in
luminal B-like tumor for distant metastasis, which resembles that in
TNBC, in contrast, AR state was stable for luminal A-like tumor even
after distant metastasis.
Conclusion: 1. The signaling via AR may surppress the distant metastasis
for TNBC and luminal B-like tumors. 2. It was suggested that there might
be at least two subpopulations in luminal-like breast cancer dependent
on the behavior in AR expression at distant metastasis.3. AR expression
was not the predicting index for the effectiveness of PST. More cases are
required to make the conclusions valid. We are studying the suppression
mechanism for distant metastasis by AR signaling.
PR149
PROGNOSTIC SIGNIFICANCE OF KI67 PROTEIN EXPRESSION IN
METASTATIC BREAST CANCER SURVIVAL
Natasa Todorovic-Rakovic, Ksenija Kanjer,
Zora Neskovic-Konstantinovic
Institute for Oncology and Radiology of Serbia, Department of
Experimental Oncology, Belgrade, Serbia
Introduction: Ki67 is a nuclear protein and established tumor proliferation biomarker with prognostic and predictive significance in breast
cancer. However there is a lack of consensus regarding its clinical use,
although it could influence selection of patients for adjuvant breast
cancer therapy. Most of the studies were focused on prognostic role
of Ki67 in early breast cancer, but its significance in metastatic breast
S73
cancer patients is less known. Aim of our study was to evaluate the
possible influence of Ki67 expression on metastatic breast cancer
survival.
Material and Methods: 84 primary tumor tissue samples with known
clinicopathological parameters, were included in the study. At the time
of diagnosis of metastatic disease, most of the patients had multiple
metastases, and the rest had single (visceral or bone) involvement.
Patients were followed from time of diagnosis of metastatic disease till
death. In metastatic setting patients received different kinds of therapy
(CMF, FAC and hormonal) single or in combination. Ki67 determination
was performed by using anti-Ki67 monoclonal antibody (clone MIB-1,
Dako, Denmark) and Ki67 index was defined as the number of Ki-67
positive nuclei per 1000 malignant tumor cells. Cutt off value of 20%
Ki67 positive cells was used.
Results: There was no correlation between Ki67 expression and the
rest of clinicopathological parameters, including steroid receptor
(ER,PR) and HER2 status. Regarding survival analysis, Ki67 expression
was independent predictor of the course of metastatic disease for the
whole group of metastatic breast cancer patients (p<0,001 Log rank
test) and especially in a subgroup of patients with tumors smaller than
2cm (T1,T2) and subgroup of patients primarily diagnosed at stage I,II
(early breast cancer). Patients with Ki67 level <20% had a much better
prognosis (median survival time 90 months) than patients with Ki67
level >/= 20% (median survival time 26 months) in a subgroup of
patients with tumors smaller than 2 cm (p=0.004 Log rank test). Also
in a subgroup of patients diagnosed at stage I,II patients with Ki67 level
<20% had a much better prognosis (median survival time 90 months)
than patients with Ki67 level >/= 20% (median survival time 24 months)
(p<0,001 Log rank test). In contrast to that, Ki67 expression was not
relevant prognostic indicator for metastatic survival in patients with
larger tumors or patients diagnosed as advanced disease.
Conclusion: This indicates that Ki67 determined from primary breast
tumor tissue could influence metastatic breast cancer survival in
favourable subgroups of patients (smaller tumor size, early stage of
disease) in a way that its increased expression mean worse prognosis
of such patients. In that context Ki67 expression could be important in
therapy decision making in adjuvant and metastatic setting as well.
PR150
PROGNOSTIC IMPACT OF 25-HYDROXYVITAMIN D LEVELS IN
EGYPTIAN PATIENTS WITH BREAST CANCER
Shereen El Shorbagy1, Rasha Haggag1, Hoda Ebian2
1
Zagazig University, Department of Medical Oncology, Faculty of Medicine,
Zagazig, Egypt; 2Zagazig University, Clinical Pathology, Faculty of
Medicine, Faculty of Medicine, Zagazig, Egypt
Background: According to the literature, vitamin D (Vit D) deficiency is
a risk factor for developing breast cancer with lack of information on its
direct prognostic effects in breast cancer.
Patients and Methods: A total of 168 women with proven breast
cancer diagnosed in Zagazig university hospitals-Egypt were enrolled
in the study. Serum level of 25(OH) Vit D was measured in stored
blood. Hydroxy vit D level classified into three groups: deficient: <
10ng/dl; insufficient: 10-30 ng/dl; and sufficient: > 30ng/dl. Clinical
and pathological data were accessed to examine prognostic effects of
vitamin D.
Results: Median age was 51.5 (26- 77) years, metastasis was present in
13.1% of the cases. Stage of tumor was I, II, III and IV in 15.5%, 34.5%,
36.9% and 13.1% 0f patients, respectively. The tumor grade was low in
11.9% 0f cases, intermediate in 63.3% of cases, and high in 26.8% of cases.
The Ki-67, HER2, ER and PR were positive in 35.7%, 32.7%, 69%, and 64.3%
of the patients, respectively. The median serum level of 25(OH) Vit D
was 20 (5-98) ng/ml; it was deficient in 39.3 % of patients, insufficient
in 32.1 % of patients, and sufficient in 31% of patients. Serum level of
25(OH)D levels decreased significantly with increasing body mass
index( BMI) (P=0.00), also the relation of 25 (OH) Vit D level with the
number of positive lymph nodes, tumor size, tumor stage and KI 67
level was statistically significant (p= 0.01,p=0.011, p=0.002, p= 0.001
S74
Abstracts / The Breast 24 S3 (2015) S21–S75
respectively). The level of 25 (OH) vitamin D was significantly lower in
metastatic patients compared to non metastatic patients (p=0.01).
Conclusion: There may be an association between deficiency in the
serum level of 25(OH) Vit D and prognosis of breast cancer.
PR151
EFFECTS OF PHYTOESTROGEN EXTRACTS ISOLATED FROM ELDER
FLOWER ON HORMONE PRODUCTION AND RECEPTOR EXPRESSION
OF TROPHOBLAST TUMOUR CELLS JEG-3 AND BEWO, AS WELL AS
MCF-7 BREAST CANCER CELLS
Lennard Schröder
University Hospital Munich, Gynecology and Obstetrics, Munich, Germany
Purpose: Lignans and flavonoids have a controversial effect on hormonedependent tumors. Herein we investigated the effect of the elderflower
extracts (EFE) on hormone production and proliferation of trophoblast
tumour cells JEG-3 and BeWo, as well as MCF-7 breast cancer cells.
Methods: The EFE was prepared and analyzed by mass spectrometry.
MCF-7, JEG-3 and BeWo cells were incubated with various concentrations
of EFE. Untreated cells served as controls. Supernatants were tested for
estradiol production with an ELISA method. Furthermore, the effect of the
EFE on ER/ER/PR expression was assessed by immunocytochemistry.
Results: The EFE was found to contain a substantial ratio of lignans.
Estradiol production was inhibited in MCF-7, BeWo and JEG-3 cells in
a concentration-dependent manner. EFE up regulates ER in JEG-3 Cell
Lines. In MCF-7 cells, a significant ER down-regulation and a significant
PR up-regulation were observed.
Conclusions: Especially the downregulating effect of EFE on estrogen
receptor expression and the up regulation of the progesterone receptor
expression in breast cancer cells are promising results of this pioneer
study. After properly designed animal studies these findings could
highlight a potential of elderflower extracts in breast cancer prevention
and/or treatment.
PR152
IS NGS STILL EFFICIENT IN FINDING NEW GENES FOR BREAST CANCER?
Aniruddh Kashyap
Pomeranian Medical University, Dept. of Genetics and Pathology, Szczecin,
Poland
Popularity of next generation sequencing (NGS) has increased
significantly in last years and it is been widely used for various types of
research approaches. We applied whole-exome sequence approach using
NGS in familial breast cancer patients from Poland. Polish population is
a homogeneous population with eleven known founder mutations in
three genes associated with breast cancer (BRCA1, CHEK2, and NBS1).
Approximately 20% of all breast cancers are of familial background and
the known founder mutations are only responsible for half of them.
We performed whole-exome sequencing in 144 selected families with
breast cancer, which were negative for eleven known Polish founder
mutations. Twenty four truncating mutations were detected in eight
known breast cancer associated genes (Cybulski et al. Clin Genet 2014). It
included new founder mutation in PALB2 gene, which was proved to be
associated with poor survival in our later studies (Cybulski et al. Lancet
Oncol 2015). Furthermore, we selected 10 other delirious mutation
in genes not yet reported to be associated with breast cancer. These
novel mutations were validated in a large series of unselected breast
cancers and controls (13,611 cases and 4,702 controls). Through this
approach, we were able to detect a new susceptibility gene for breast
cancer (RECQL) with an odds ratio of 5.4 (p=0.008) (Cybulski et al. Nat
Genet 2015). Therefore we concluded that the whole-exome sequencing
approach using NGS in genetically homogeneous populations is efficient
in finding novel mutation and new genes associated with breast cancer.
PR153
VITAMIN D IMPORTANCE IN THE ONCOLOGY CONSULTATION FOR
THE BREAST CANCER PATIENT
Vasco Fonseca1, Margarida Brito2, Sofia Cassamo1, Daniel Sousa1,
Daniel Romeira1, Ana Martins1
1
CHLO, Oncology Department, Lisboa, Portugal; 2IPO de Lisboa, Oncology
Department, Lisboa, Portugal
Introduction: The relation between vitamin D and breast cancer is
not yet totally defined and there is no consensus about its role in the
disease’s etiopathogenesis. Literature allude that a low laboratorial
value of vitamin D3 (25-hydroxicholecalciferol) is related with a higher
risk of breast cancer, as well as with a worse prognostics in these
patients. In patients treated with aromatase inhibitors, RANKL inhibitors
or biphosphonates it is defined that they should do the calcium and
vitamin D supplementation, but it is not yet defined, in this patients’
subgroup, if its dosing should be considered. The link between breast
cancer and bone disease is well known, and it is compulsory in the
oncology and clinic setting, a specific approach to these patients’ bone
pathology. Once more, it is not defined, for all the sceneries, the part of
calcium and vitamin D’s supplementation, nor the value of vitamin D’s
laboratorial dosage.
Objectives: To describe the laboratorial value of vitamin D in Breast
Cancer patients, in clinical practice.
Material and Methods: In an oncology consultation, in the Western
Lisbon Hospital Centre, there was a selection of the patients who,
randomly were asked to get the vitamin D’s dosage, between the 1st of
January 2014 and the 21st of April 2015, before the calcium and vitamin
D’s supplementation.
Discussion: From a universe of 56 examined patients (44 adjuvant
therapy and 12 metastatic disease), it was concluded that 27 had vitamin
D3’s dosage. The median age was 64 years with a range from 31 to 97
years. Within these 27 patients, 1 had a result <25 nmol/L (deficient),
24 patients between 25 and 75 nmol/L (insufficient), 2 between 75 and
250 nmol/L (normal) and none of them with values above 250 nmol/L
(toxic). The average concentration of vitamin D3 in these patients was
48.6 nmol/L, with a maximum value of 82 nmol/L and a minimum less
than 20 nmol/L. The five patients with metastatic disease that realize
vitamin D had average concentration of vitamin D3 of 39 nmol/L.
The two patients with normal values in the vitamin D’s dosage were
supplementing it before the consultation.
Conclusion: It is considered that, in breast cancer patients, vitamin D’s
dosage should be performed in the first oncology consultation and that
this value should be taken into consideration to decide if there will be a
supplementation. It is also acknowledged that rules should be created,
for clinical orientation, regarding situations in which the vitamin D’s
dosage should be performed and its frequency. It should be clarified the
vitamin D’s supplementation in its individual form or with calcium, for
breast cancer patients, in an adjuvant strategy or for metastatic disease.
PR154
EVALUATION OF CARDIOTOXICITY IN BREAST CANCER PATIENTS
WITH HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2
OVEREXPRESSION UNDERGOING TRASUZUMAB TREATMENT
Nicoleta Zenovia Antone
Institute of Cancer “Prof dr. Ion Chiricuta”, Dept. of Radiotherapy, ClujNapoca, Romania
Objective: Evaluation of cardiotoxicity in patients with breast cancer
overexpressing the human epidermal growth factor receptor-2 in the
setting of treatment with transtuzumab.
Material and Methods: The study observed 31 patients (medium
age 52.16±8.2 years; 30 females and 1 male) diagnosed with breast
carcinoma overexpressing the human epidermal growth factor
receptor-2 and following treatment with trastuzumab. Assessment of
cardiovascular status and echocardiography was performed initially
Abstracts / The Breast 24 S3 (2015) S21–S75
and at 3, 6, 9, 12 and 18 months. Several demographic, clinical and
paraclinical parameters of patients were observed. Cardiotoxicity was
defined as: 1) an absolute drop ≥10% in the final left ventricular ejection
fraction from the baseline value and below the level of 50% , 2) each
absolute decrease of the final left ventricular ejection fraction ≥15% in
any moment of the evaluation, 3) any symptoms or signs of heart failure.
Results: The study observed 6 cases (19.4%) that performed the criteria
for cardiotoxicity. Asymptomatic diastolic dysfunction was present
in 9 patients (29%). There were no statistically significant variations
of the final left ventricular ejection fraction in different moments of
the evaluation (p=0.23). The age of the patients had no influence on
cardiotoxicity (p=0.36). Cardiac toxicity was not statistical associated
S75
with the performance status ECOG (p=0.11), stage of disease (p=0.56),
history of arterial hypertension (p=0.2), diabetes mellitus (p=0.64),
obesity (p=0.95), dyslipidemia (p=0.15), prior anthracycline exposure
(p=0.95), concomitant treatment with taxanes (p=0.35), prior leftsided radio-therapy (p=0.38) and asymptomatic diastolic dysfunction
(p=0.64). The median age of the patients who developed asymptomatic
diastolic dysfunction during treatment with trastuzumab (58.33±5.41)
was significantly higher than the median age of the patients without the
condition (49.64±7.87) (p=0.005).
Conclusions: One out of five treated patients developed cardiotoxicity.
None of the studied parameters had any influence on cardiac toxicity in
the study group.
The Breast 24 S3 (2015) S76–S77
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
ABC3 - Disclosure of Conflict of Interest
Faculty members have been asked to disclose any potential
conflict of interest in relation to their participation in the
conference. Potential conflict of interest are considered any of
the following:
• Any financial interest in or arrangement with a company
whose products or services are discussed in the lecture or that
might be considered as part of the consensus process.
• Any financial interest in or arrangement with a competing
company.
• Any other financial relationship, direct or indirect, or other
situations that might raise the question of bias in the work
presented or in the participation in the consensus process,
including pertinent commercial or other sources of funding
for the speaker or panellist or for the associated department
or organisation, personal relationships or direct academic
competition.
ABC3 chairs, faculty and panel members
Matti Aapro: Consultant for Abraxis, Amgen, BMS,
CarisLifeSciences, Celgene, Eisai, GenomicHealth, GSK,
Helsinn, Hospira, Novartis, Merck, Merck Serono, Pfizer,
Pierre Fabre, Roche, Sandoz, Teva, Vifor and has received
honoraria for lectures at symposia f Amgen, Astellas, Bayer
Schering, Cephalon, Eisai, Ferring, Genomic Health, GSK,
Helsinn, Hospira, Ispen, JnJ OrthoBiotech, Merck, Merck
Serono, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi,
Teva, Vifor
Fabrice Andre: No significant relationships
Samuel Aparicio: Receipt of grants/research supports: Takeda
Biopharma
Carlos H. Barrios: Receipt of grants/research supports: Amgen,
Astra Zeneca, Boehringer-Ingelheim, GSK, Novrtis, Pfizer,
Roche/Genentech, Eisai, Lilly, Sanofi-Aventis, Celgene and has
received honoraria or consultation fees from: BoehringerIngelheim, GSK, Novartis, Pfizer, Roche/Genentech
Marc Beishon: Receipt of honorarium: Pfizer
Jonas Bergh: Receipt of grants/research supports paid to
Karolinska Institute and University Hospital: Roche, Bayer,
Sanofi-Aventis, Astra Zeneca, Pfizer, Merck, Amgen
Gouri Shankar Bhattacharyya: No significant relationships
Laura Biganzoli: No significant relationships
Fatima Cardoso: Receipt of honoraria or consultation fees:
Astellas/medication, Astra Zeneca, Celgene, Daiichi-Sankyo,
Eisai, GE Oncology, Genentech, GSK, Merck-Sharp, Merus BV,
Novartis, Pfizer, Roche, Sanofi
Maria-João Cardoso: No significant relationships
Lisa A. Carey: No significant relationships
Dian “CJ” M. Corneliussen-James: Receipt of honoraria for
work for ABC3
Alberto Costa: No significant relationships
Robert E. Coleman: Receipt of grants/research supports: Bayer,
Celgene. Expert testimony: Novartis
Giuseppe Curigliano: No significant relationships
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Véronique Dieras: Receipt of honoraria or consultation
fees: Roche, Genentech, Novartis, Eisai. Participation in a
sponsored speakers bureau: Roche, Pfizer
Nagi S. El Saghir: Receipt of grants/research supports: GSK,
Novartis, Roche. Receipt of honoraria or consultation fees:
lecture honoraria: Novartis, Roche, MSD, AstraZeneca,
Celgene
Alexandru Eniu: Receipt of grants/research supports: Astra
Zeneca, Roche, Celltrion, Pfizer, Mylan
Lesley Fallowfield: No significant relationships
Doris Fenech: No significant relationships
Patrick Flamen: Receipt of grants/research supports: Sirtex/
Bayer, receipt of honoraria or consultation fees: Sirtex/Bayer
Prudence A. Francis: Conference travel support from Roche and
Amgen
Karen Gelmon: Receipt of honoraria or consultation fees:
Roche, Genetech, Astra Zeneca, Pfizer, Nanostring, Novartis
Alessandra Gennari: Receipt of grants/research supports:
Celgene/Teva, receipt of honoraria or consultation fees:
Celgene, Teva, Eisai, Pierre Fabre, participation in a
sponsored speakers bureau: Celgene, Teva, Eisai
Nadia Harbeck: Receipt of honoraria or consultation fees:
Amgen, Astra Zeneca, Celgene, Novartis, Pfizer, Roche
Jens Hoffmann: Employee or stock shareholder: EPO—
Experimental Oncology and Pharmacology Berlin-Buch
GmbH, Bayer Pharma AG
Clifford Hudis: No significant relationships
Bella Kaufman: Receipt of honoraria: AstraZeneca, Novartis,
Pfizer and Roche
Ian E. Krop: Receipt of grants/research supports: Genentech/
Roche
Stella Kyriakides: No significant relationships
Musa Mayer: No significant relationships
Hanneke Meijer: No significant relationships
Shirley A. Mertz: Receipt of honoraria or consultation fees: Pfizer
Larry Norton: No significant relationships
Shinji Ohno: No significant relationships
Olivia Pagani: Participation in a sponsored speakers bureau:
Novartis, Celgene
Evi Papadopoulos: No significant relationships
Fedro A. Peccatori: No significant relationships
Frédérique Penault-Llorca: No significant relationships
Martine J. Piccart: Board member: PharmaMar; consultant
(honoraria: Amgen, Astellas, AstraZeneca, Bayer, Eli Lilly,
Invivis, MSD, Novartis, Pfizer, Roche-Genentech, Sanofi
Aventis, Symphogen, Synthon, Verastem; research grants to
my institute most companies
Jean-Yves Pierga: Receipt of grants/research supports: Roche,
Jansen Diagnostics; receipt of honoraria or consultation
fees: Roche, GSK, Novrtis, Genomic Health; participation in a
sponsored speakers bureau: Roche, Novartis
Fausto Roila: No significant relationships
Hope S. Rugo: receipt of grants/research supports: GSK,
Genentech/Roche, Novartis, Merck, Pfizer, Eisai, Macrogenics,
Amgen, Biomarin, Plexxikon
Conflict of interest / The Breast 24 S3 (2015) S76–S77
Kimberly A. Sabelko: No significant relationships
Elzbieta Senkus-Konefka: Receipt of honoraria or consultation
fees: Astellas, Janssen, Bayer, Roche, AstraZeneca, GSK,
Amgen, Pierre Fabre, Teva; travel expenses: Roche, Novartis,
Janssen, Astellas, Amgen, Sandoz, Ipsen, Bayer, Egis
Lille D. Shockney: No significant relationships
George W. Sledge Jr.: Member Board of Directors: Syndax;
member SAB: Symphogen
Danielle Spence: No significant relationships
Richard Sullivan: Receipt of unrestricted research grant
Sandra Swain: Receipt of grants/research supports: Genentech/
Roche, Pfizer, Puma; receipt of honoraria or consultation
fees: Genentech/Roche, Clinigen, Astra Zeneca; participation
in a sponsored speakers bureau; nonpromotional Genentech/
Roche; spouse/partner: travel: Genentech/Roche; travel:
Genentech/Roche
S77
David G. Taylor: Receipt of grants/research supports: Novartis;
receipt of honoraria or consultation fees: Novartis
Christoph Thomssen: No significant relationships
Luzia Travado: Receipt of honoraria or consultation fees:
Novartis and Roche
Andrew Tutt: Receipt of grants/research supports: Vertex,
Astra Zeneca, Myriad Genetics, Roche; receipt of honoraria
or consultation fees: Verte, Eisai; named on patent (King’s
College London) Genome Instability; rewards to Inventors
Scheme- Institute of Cancer Research ARP inhibitors BRCA1/2
Associated Cancers
Daniel A. Vorobiof: No significant relationships
Eric Winer: Receipt of grants/research supports: Genentech/
Roche
Binghe Xu: No significant relationships
The Breast 24 S3 (2015) S78–S81
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Author index
Aaltonen, K.
Aapro, M.
Abdalla, S.
Abedini, M.R.
Abou-Shousha, S.A.
Agresti, R.
Ahn, E.
Akagi, Y.
Alieldin, N.
Amadori, D.
Amaducci, L.
Amendoeira, I.
Amina, T.
André, F.
Anikusko, M.
Antone, N.Z.
Antunez de Mayolo, J.
Anwar, M.M.
Aparicio, S.
Aranda, S.
Arata, R.
Arihiro, K.
Arisanty. D,
Arju, R.
Arora, S.
Artamonova, E.
Asghari, F.
Awad, A.T.
Aziz, B.
Azmi, R.
PO143
IN22, PO112
PO110
PO144
PO132
BP103
PR118
OR128
PO77
BP129
BP129
PO138
PO83
IN12
PO109
PR154
PR118
PO132
IN24
PO40
PO104
PO104
PO135
PO133
IN03
PO55
PR137
PO66
PO97
PO41
Bachelot, T.
Balena, F.
Bardenhewer, M.
Barrios, C. H.
Basha, A.M.
Battley, J.E.
Beamish, R.
Beaumont, T.
Bebeci-Docaj, A.
Bell Dickson, R.
Belyaeva, A.
Bendahl, P.
Benn, C.A.
Bergh, J.
Berrada, N.
Bhattacharyya, G.S.
Bianchi-Micheli, G.
Bidard, F-C.
Bidoli, P.
Bilic, I.
Bird, B.R.
Bologna, A.
Bolotina, L.V.
Bonadies, A.
Borg, C.
Botella, A.
Bozic, M.
Bozovic-Spasojevic, I.
Brady, C.
Bragato, B.
Brechenmacher, T.
Brito, M.
Broco, S.
PO56
PO43
BP52
IN09
PO66
PO145
PO145
PO48
PR90
PO42
PR136
PO143
PO106, PO108
IN14
PO83, PR126
IN35
PO117
IN23
PO64
PR94
PO145
BP129
PO107
BP103
PO110
PO116
PO99
PO58, PO59
PO69
PO43
PO56
PR153
PO68, PO70
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Bruzzi, P.
Busko, E.
Bussone, R.
BP129
PR136
BP103
Cabula, C.
Cameselle-Teijeiro, J.
Campana, L.
Campos, L.
Canario, R.
Cardoso, D.
Cardoso, F.
Cardoso, M-J.
Carey, L. A.
Carvalho, T.
Casalta-Lopes, J.
Cassamo, S.
Catarino, A.
Cazzaniga, M.E.
Chamalidou, C.
Chari, N.
Cherdyntseva, N.
Cheshuk, V.
Ciccarese, M.
Clivio, L.
Coate, L.
Coleman, R.
Collins, R.
Conti-Beltraminelli, M.
Coons, H.L.
Córdoba Ortega, J.F.
Corneliussen-James, CJ Dian.
Cortesi, L.
Crawford, K.
Cropley, M.
Crowne, J.P.
Cruz, J.
Cubano, L.A.
Cunha, J.
Curatolo, P.
Curigliano, G.
BP103
PO138
BP103
PO116
PO70
PO116
PO56
IN29
IN15
PO68, PO70
PO70
PR153
PO68
PO64
PO96
BP38
PR147
PO109
PO64
PO64
PO145
IN01
PO69
PO117
PO42
PO142
IN02
PO64
OR37
PR124
PO145
PO70
PO133
PO78, PR95
BP103
IN17
D'Aiuto, M.
Darwish, A.
de Lara, S.
De Laurentiis, M.
De Meo, L.
Debled, M.
De Censi, A.
Decio, R.
Decker, T.
Del Mastro, L.
Della Torre, S.
Dellepiane, C.
Denisov, E.
Diéras, V.
Dionisio, M.R.
Duffy, K.A.
BP103
PO77
PO96
BP103
BP103
PO56
BP129
PO117
OR51
PO62
PO64
PO62
PR147
IN13
PO138
PO145
Ebian, H.
Ebrahimpour Koujan, S.
Elhussini, M.A.
El-hussieny, G.
El Shorbagy, S.
Eniu, A.
PR150
PR137
PO66
PO66
PR150
IN07
Author index / The Breast 24 S3 (2015) S78–S81
Enlund, F.
Esser, M.
PO96
PO45, PO115
Fabrizio, T.
Fadoua, E.
Fallowfield, L.
Fancelli, S.
Farci T.
Farhat, F.
Feliz-Mosquea, Y.
Fernandes, L.
Ferreira, A.
Ferzi, A.
Flamen, P.
Fonseca, V.
Fonseca, C.
Fouzia, M.
Franci, S.
Francis, P.A.
Freitas, D.
Freschi, A.
Fujihara, M.
Furtado, I.
BP103
PR126
IN10
PO62
PO43
PO61
PO133
PO116
PO62
PO64
IN19
PO116, PR153
PO116
PR126
PO43
IN27
PO78, PR95
BP129
PO53
PO79
Gabrys, D.
Galuppo, S.
Gasol Cudos, A.
Gebhart , G.
Gehring, C.
Gelmon, K.
Gennari, A.
Gerashchenko, T.
Gervásio, H.
Ghosn, M.
Gianni, L.
Giashuddin, S.
Gilmore, J.
Ginsberg, S.
Giovanardi, F.
Gisbert, R.
Goga, A.
Gojkovic Horvat, A.
Gomes, M.
Gonçalves, B.
Gorini, A.
Gosalbez, B.
Gough, K.
Govindbabu K.
Grasso, D.
Grilz, G.
Gugic, J.
Guida, M.
Güth, U.
Gyr, T.
PO98, PO100
BP103
PO142
IN19
BP52
IN05
IN28, BP129
PR147
PO68, PO70
PO61
BP129
PO133
PO69
PO46
PO64
PO142
PO134
PO99
PO138
PO68, PO70
PR124
PO79
PO40
IN35
PO62
BP103
PO99
BP103
PO63, PO75, PO81, PR91, PO105
PO117
Haggag, R.
Hakamada, K.
Hamza, E.
Hanane, R.
Hansra, D.
Harahap, W.A.
Harbeck, N.
Harmer, V.
Harrold, E.
Hassan, E.
Hayama, S.
Hegg, R.
Helal, A.
Hennessey, B.
Herz, S.
Hikichi, M.
Hind, M.
Hiroki, O.
Hoffmann, J.
Hoshyar, R.
Huang, D.
Hudis, C.A.
Hurlbert, M.
PR150
PO76
PR126
PR126
PR118
PO135
IN26, BP52
PO42
PO69, PO122
PO83, PR126
PO80, PO101
PO56
PO77
PO145
PO73, PO141
PO57
PO83, PR126
PO74
IN25
PO144
PO63 PO75 PO81 PR91 PO105
IN18
OR37
S79
Ibragimov, J.
Ibrahim, E.
Ide, R.
Igawa, A.
Ikebe, D.
Imane, O.
Imoto, S.
Imyanitov, E.
Irfan, M.
Isaka, H.
Ishida, K.
Ishige, H.
Ishikawa, M.
Ismail, J.R.M.
Itami, M.
Itamoto, T.
Ito, H.
Ito, M.
Itoh, K.
Iwakuma, N.
Iwase, T.
PO114
PO83, PR126
PO104
PO76
PO72
PR126
PO130
PR136
PO97
PO130
PR93
PR123
PR85
PO145
PO72
PO104
PO130
PO53
OR128
OR128
PO80
Jänicke, M.
Jansson, S.
Jarz b, M.
Jung, S.
Jwa, E.
OR51
PO143
PO98
PR146
PR146
Kadirova, Z.
Kadoya, T.
Kajiwara, Y.
Kanauchi, H.
Kanjer, K.
Kashiwaba, M.
Kashyap, A.
Katcharava, M.
Katselashvili, L.
Kattan, J.
Kawagishi, R.
Keane, M.
Kelly, C.M.
Kelly, L.
Kennedy, M.J.
Khambri. D,
Khasanova, A.
Kikuchi, Y.
Kim, J.Y.
Kim, T.H.
Kim, Y.
Klimenko, V.
Knackmuhs, V.
Knox, S.
Kobakhidze, S.
Kobayashi, N.
Kolarevic, D.
Kolben, T.
Kolberg, G.
Komatsu, H.
König, A.
Kovács, A.
Kovalenko, E.
Koynov, K.
Krivorotko, P.
Krop, I.E.
Kruggel, L.
Kulik, R.
Kumar, D.
Kunstmann, G.
Kunze-Busch, M.
Kurbacher, A.T.
Kurbacher, C.M.
Kurbacher, J.A.
PR113
PO104
PO53
PO54
PR149
PR93
PR152
PO67
PO67
PO61
PR93
PO145
PO145
PO69
PO145
PO135
PR88
PO54
PR146
PR146
PR146
PR136
OR37
PO39
PO67
PO57
PO59, PR89
BP52
PO73
PR93
BP52
PO96
PO55
PO82
PR136
IN04
OR51
PO100
PR102
PO141
IN20
PO73
PO73, PO141
PO73, PO141
Lacerda, M.
Lai, A.
Lambertini, M.
Larsson, A-M.
PO138
PO62
PO62
PO143
S80
Author index / The Breast 24 S3 (2015) S78–S81
Larysz, D.
Leadbeater, M.
Lee, E.S.
Lee, K.S.
Li, J.
Linderholm, B.
Liubota, I.
Liubota, R.
Llombar Cussac, A.
PO98
PO48
PR146
PR146
PO139
PO96
PO109
PO109
PO142
Macneal, P.
Madeira, P.
Majdic, E.
Makhamedjanov, D.
Malhotra, H.
Manlius, C.
Manna, A.
Manzyuk, L.
Mapunda, P.
Mariano, M.
Marinko, T.
Marques, A.
Marschner, N.
Martin, M.J.
Martinez-Montemayor, M.M.
Martins, A.
Marven, M.
Marx-Rubiner, L.
Masaki, T.
Matias-Guiu Guia, X.
Matsubara, K.
Matsui, Y.
Matsuo, S.
Matsuura, K.
Mayer, M.
McCann, M.
McNamara, B.
Meani, F.
Mehmood, T.
Mehta, A.
Meijer, H.J.M.
Melo Cruz, F.
Mertz, S.A.
Michishita, S.
Miguens, M.
Mihanfar, A.
Milosevic, S.
Milovic-Kovacevic, M.
Minuti, G.
Mishima, M.
Miwa, N.
Miyaki, T.
Miyamoto, K.
Miyazaki, M.
Mohammed, L.
Monreal, K.
Montagna, G.
Moodley, S.
Moral, D.
Morales Murillo, S.
Moriconi, T.
Morimoto, T.
Mostafavinia, E.
Mubarikha, S.
Mueseler, S.B.
Mukhametshina, G.
Münz, M.
Mura, S.
Murakami, S.
Murphy, C.G.
Murphy, J.
Murphy, V.
Myasnyankin, M.J.
PO110
PO68, PO70
PO99
PR113
IN35
PO56
PR50, PR120, PR121
PO55
PO106
PO68, PO70
PO99
PO78, PR95
OR51
PO145
PO133
PO116, PR153
PO40
PO44
PO74
PO142
PO104
PR93
PO60
PO104
OR37
PO45, PO115
PO69
PO117
PO97
PR118
IN20
PO56
IN06, OR37
PR87
PO116
PR137
PO58, PO59
PO140
PO62
OR128
PR148
PO72
PO130
PO80
PR126
PO73
PO117
PO108
PO142
PO142
PO43
PR87
PO144
PO135
PR49
PR88
OR51
PO62
PR85
PO145
PO122
PO145
PR111
Nabiço, R.
Nagano, O.
Nagashima, T.
PO78, PR95
PO101
PO80, PO101
Nakai, M.
Nakamura, R.
Nakamura, S.
Namysł-Kaletka, A.
Nanni, O.
Nasr, O.M.
Nayler, S.
Neric, D.
Neskovic-Konstantinovic, Z.
Nighat, S.
Nilsson, J.
Ninashvili, N.
Nishi, T.
Nishimura, A.
Nishioka, K.
Niwa, T.
Nobre Carvalho, A.
Noma, M.
Novikov, S.
Nusch, A.
PR84
PO72, PO101
PR148
PO100
BP129
PO132
PO108
PO59
PR149
PO97
PO71
PR125
PO76
PO76
PO54
PO54
PO79
PO104
PR136
OR51
O'Connor, M.
O'Donoghue, N.
Ohtani, S.
Okabe, M.
Okada, M.
Okano, K.
O'Leary, C.
O'Mahony, D.
Onishi, T.
O’Reagan, K.
O'Reilly, S.
Otsuki, H.
PO145
PO69
PO53
OR128
PO104
PO76
PO69
PO69, PO145
PR148
PO122
PO69, PO122, PO145
PR93
Pagani, O.
Pais, A.
Paleari, L.
Panaccione, M.
Papadopoulos, E.
Paredes, J.
Parikh, P. M.
Park, I.H.
Paulin Kosir, M.S.
Pazos, I.
Pêgo, A.
Pereira, J.
Perelmuter, V.
Perez-Laspiur, J.
Pierga, J-Y.
Poggio, F.
Poletto, E.
Policiti, I.
Poortmans, P.
Portela, C.
Pozzi, E.
Pramod, S.
Pravettoni, G.
Pronzato, P.
Provinciali, N.
Pugliese, P.
Puglisi, F.
Pulatov, D.
Puntoni, M.
IN30, PO117
PO68, PO70
BP129
PO43
IN32
PO138
IN35
PR146
PO99
PO68, PO70
PO68, PO70
PO116
PR147
PO133
IN23
PO62
PO62
PO43
IN20
PO78, PR95
PO62
PO47, PR92, PR119
PR124
PO62
IN28, BP129
PO64
PO62
PO114
BP129
Quade, A.
Queiróz, L.
PO141
PO78
Ramdial, J.
Rammohan, P.
Ranada, A. A .B.
Rashid, A.
Ratosa, I.
Ratti, V.
Rayne, S.
Reis, C.
Renne, M.
Ri, Y.
PR118
PO65
IN35
PO97
PO99
PO117
PO106
PO79
BP103
PO57
Author index / The Breast 24 S3 (2015) S78–S81
Ringeisen, F.
Risi, E.
Riva, S.
Rizk Demian, S.
Rizzi, G.
Ro, J.
Rocca, A.
Roila, F.
Romeira, D.
Rossi, G.
Rossi, L.
Rowe, J.
Royce, M.
Rugo, H.S.
Ruiz, D.
Rydén, L.
PO56
PO62
PR124
PO132
PO112
PR146
BP129
IN21
PR153
PO112
PO117
PO45, PO115
PO56
IN08, PO112, PO134, PO139
PR118
PO143
Saber, B.
Safina, S.
Sakakibara, M.
Sakamoto, M.
Salud Salvia, A.
Samame Pérez-Vargas, J.C.
Sampayo, I.
Sangai, T.
Santoriello, A.
Sarcevic, A.
Sato, M.
Schmid, S.
Schmitt, F.
Schneider, R.J.
Schoenfeldt, A.
Schötzau, A.
Schröder, L.
Schweitzer, C.
Semiglazov, V.
Semiglazov, V.
Semiglazova, T.
Serrate López, A.
Sesek, M.
Shah, M.A.
Shavdia, M.
Shiina, N.
Shijijo, S.
Shin, K.H.
Shirakawa, K.
Shockney, L. D.
Shunji, K.
Madeira, P.
Sini, V.
Sledge, G.W.
Sobhy El Sedafi, A.
Solari, N.
Soliaman, L.
Sottotetti, F.
Sousa, D.
Sousa, G.
Spence, D.
Stamatovic, L.
Stanic, N.
Stockunas, A.
Suarez-Arroyo, I.J.
Sueoka, S.
Sukhotko, A.
Sullivan, R.
Sundén, M.
Sundquist, M.
Susnjar, S.
Sutliff, M.
PO83, PR126
PR88
PO80
PO101
PO142
PO142
PO42
PO80
BP103
PO59
PO131
PO63, PO75, PO81, PR91, PO105
PO138
PO133
PO96
PO75, PO81, PO105
PR151
PO73
PR136
PR136
PR136
PO142
PO99
PO97
PR125
PO72
OR128
PR146
PO54
IN31
PO74
PO68, PO70
PO62
IN36
PO132
BP103
PO77
PO62
PR153
PO68, PO70
PO40
PO140
PO58
PO145
PO133
PO104
PO107
IN33
PO96
PO71
PO58, PO140
PO45, PO115
S81
Swain, S.M.
IN03
Tada, K.
Tanaka, H.
Tanaka, K.
Taushanova, M.
Taylor, D.
Tejler, G.
Thorne, S.
Thulin, A.
Timcheva, K.
Todorovic-Rakovic, N.
Toh, U.
Tomasevic, Z.
Tomasevic, Z.
Torri, V.
Traina, T.
Trela-Janus, K.
Turkevich, E.
Tutt, A.
PO54
PR85
PR85
PO82
IN34
PO71
IN05
PO96
PO82
PR149
OR128
PO59
PO58, PO59, PR89
PO64
IN18
PO100
PR136
IN16
Uchida, Y.
Uchiyama, A.
Ueno, T.
Umeda, S.
Ushimado, K.
Utsumi, T.
PO54
PR85
PO130
PR85
PO57
PO57
Vacca, I.
Valls, J.
Valpione, S.
Vanacker, L.
Velasco Sánchez, A.
Venter, M.
Vereshchako, R.
Vicente de Paulo, J.
Vidal, J.
Vidula, N.
Vieira, A.F.
Volchenko, A.A.
Villanueva, C.
PO43
PO142
BP103
PR86
PO142
PO108
PO109
PO68
PO142
PO134, PO139
PO138
PO107
PO56
Wakeda, T.
Walker, D.
Wallberg, M.
Walshe, J.M.
Warm, M.R.
Watanabe, J.
Werner-Rönnerman, E.
Widera, K.
Würstlein, R.
Wzietek, I.
PO54
PO45, PO115
PO96
PO145
PO141
PO60
PO96
PO98, PO100
IN26, BP52
PO100
Yamada, A.
Yamamoto, M.
Yamamoto, N.
Yamamura, J.
Yanwirasti,
Yau, C.
Yoshida, E.
Yoshimura, Y.
Yutaka, K.
OR128
PO104
PO72, PO101
PO74
PO135
PO134, PO139
PO76
PO53
PO74
Zavyalova, M.
Zdravko, Z.
Zikiryahodjaev, A. D.
Ziliani, S.
Zrelykh, L.
PR147
PO59
PO107
PO62
PR127
The Breast 24 S3 (2015) S82–S85
Contents lists available at ScienceDirect
The Breast
j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / b r s t
Abstracts List
Invited abstracts
IN01
IN02
IN03
IN04
IN05
IN06
IN07
IN08
IN09
IN10
IN12
IN13
IN14
IN15
IN16
IN17
IN18
IN19
IN20
IN21
IN22
IN23
IN24
IN25
IN26
IN27
IN28
IN29
IN30
IN31
IN32
IN33
IN34
IN35
ABC3 Award Abstract: Living with metastatic bone disease – the positive impact of bone-targeted treatments
Metavivor: Fighting prejudice
Is there an optimal treatment sequence for HER2 positive advanced breast cancer?
Optimal management of HER-2+ ABC
Long term survival with advanced disease. challenges for the patient, their support system and care givers
Living on borrowed time: long term responders
New drugs, new side effects: endocrine side effects
Treatment associated risks: identifying and treating pulmonary toxicity
Toxicity of modern immunotherapy approaches
The role of patient reported outcomes
The role of CDK and PI3K/MTOR inhibitors
Revolutionizing ER+ ABC management: ESR1 and other suspects in resistance
Is ovarian ablation mandatory in pre-menopausal ER+ ABC patients?
Optimal management of triple negative metastatic breast cancer (today)
Resurrecting parp inhibition
Can immune-based therapies be the key?
Triple negative breast cancer: the role of androgen receptor and its inhibitors
Imaging receptor expression and glycolytic activity using PET-CT to individualize treatment in metastatic HER2 positive breast cancer (MBC)
Towards improved disease outcome combined with a reduction of toxicity using new radiation therapy techniques
Optimal management of fatigue
Dyspnea: the hardest symptom to control?
Circulating tumor cells and tumor DNA: are liquid biopsies a dream?
Clonal evolution in breast cancer patients and patient derived xenografts
Patient xenograft models: can an "avatar" help?
Biopsy, rebiopsy and dealing with discordant results in ABC
Advanced breast cancer: is there an optimal sequence of systemic anticancer agents?
Duration of first-line chemotherapy in metastatic breast cancer
Surgery of the primary tumour: should the recommendation be changed?
Survivorship in ABC: which are the main issues?
Addressing the emotional needs of patients with advanced metastatic breast cancer
Living with MBC is like walking on a tight rope, a balancing act using all resources, to hold on and reach the other end
The cost of breast cancer: a global perspective
Breast cancer care access and affordability: are drugs the main issue in Europe?
Can we really apply international guidelines in limited resources countries?
Abstracts - Nursing and Advocacy
OR37
BP38
PO39
PO40
PO41
PO42
PO43
PO44
PO45
PO46
PO47
PO48
PR49
PR50
Unmet psychosocial and quality of life needs of patients living with metastatic
Metastatic breast cancer in Canada: waiting for treatment
Effective advocacy for women with metastatic breast cancer: a European perspective
Unmet needs of Australian women with metastatic breast cancer with financially dependent children: the consumer perspective
Middle Eastern ABC/MBC Patients: overcoming the triple-burden of stigmatization, lack of information and recurrent illness
Make Your Dialogue Count Survey: addressing communication gaps between patients with advanced breast cancer, their caregivers and
oncologists and understanding information and emotional needs to improve treatment and side effect management
“Fight, live, keep smiling”: the first Italian blog about metastatic breast cancer (MBC) addressed to the general public. A quali-quantitative
analysis of all the comments posted online on the blog of the Europa Donna Italia MBC Working Group
In Our Shoes: raising the voices of MBC patients
Information needs of young women with metastatic breast cancer to manage their treatment, side effects and clinical trials
I AM ANNA: Exploring metastatic breast cancer through the eyes of a young woman
Identifying deficits and needs from stakeholders about palliative care issues
Terminology used in advanced breast cancer and the need for consistency
Getting back into life
Psychological support to cancer patient through volunteers & survivors
0960-9776/© 2015 Elsevier Ltd. All rights reserved.
Abstract list / The Breast 24 S3 (2015) S82–S85
S83
Abstracts – Clinical Issues : Medical Oncology
OR51
BP52
PO53
PO54
PO55
PO56
PO57
PO58
PO59
PO60
PO61
PO62
PO63
PO64
PO65
PO66
PO67
PO68
PO69
PO70
PO71
PO72
PO73
PO74
PO75
PO76
PO77
PO78
PO79
PO80
PO81
PO82
PO83
PR84
PR85
PR86
PR87
PR88
PR89
PR90
PR91
PR92
PR93
PR94
PR95
No impact of increasing symptoms on quality of life? Longitudinal data from the German MALIFE-Project on patients receiving
monochemo- and endocrine treatment for advanced breast cancer – results from the TMK registry group
Is there a different treatment response between visceral and non-visceral metastatic breast cancer: a systematic literature review of
registration trials
Clinical impact of metronomic oral combination chemotherapy with capecitabine and cyclophosphamide in patients with metastatic breast
cancer
A retrospective multicenter observation study in metastatic breast cancer patients: comparative analysis on efficacy of eribulin mesylate
with taxane regimens (including combination with bevacizumab)
Efficacy and safety of eribulin in anthracycline and taxane-pretreated patients: Russian experience
BOLERO-4: A phase 2, open-label, multicenter, single-arm trial investigating the efficacy and safety of first-line everolimus (EVE) in
combination with letrozole (LET) in postmenopausal patients (pts) with estrogen receptor–positive (ER+), human epidermal growth factor
receptor 2–negative (HER2–) metastatic or locally advanced unresectable breast cancer (BC)
Clinical efficacy of LH-RH analogue plus aromatase inhibitor in premenopausal women with estrogen receptor–positive advanced breast
cancer: a single-institution retrospective study
Does previous neoadjuvant/adjuvant trastuzumab influence the disease outcome of metastatic HER2 positive breast cancer patients treated
with first line trastuzumab and chemotherapy
Durable remissions with trastuzumab treatment for HER2 positive metastatic breast cancer – single center experience
The role of lapatinib in the management of HER2-positive metastatic breast cancer: a review of a single institution’s experience during the
trastuzumab and lapatinib era
Oral vinorelbine in combination with trastuzumab as a first line therapy of metastatic or locally advanced Her2-positive breast cancer
First line trastuzumab-based therapy in HER2-positive metastatic breast cancer patients presenting with de novo or recurrent disease: a
multicenter retrospective cohort study
Cure in metastatic breast cancer: an aggressive approach does not appear to be the key to the black box
Metronomic chemotherapy (CHT) combination of vinorelbine (VRL) and capecitabine (CAPE) in HER2- advanced breast cancer (ABC)
patients (pts) does not impair Global QoL. First results of the VICTOR-2 study
Phase II trial of metronomic combination chemotherapy with oral regimen in heavily pretreated metastatic breast cancer
Neoadjuvant chemotherapy for locally advanced breast cancer; a solution to avoid mastectomy
Neo-adjuvant hormonal therapy for locally advanced breast cancer
Triple negative breast cancer - Neoadjuvant chemotherapy response evaluation with taxane/anthracycline protocol - Single centre 5 years
experience.
Brachial plexopathy in metastatic breast cancer: a review of patient characteristics and diagnosis in an Irish tertiary referral centre.
Estrogen receptor as a negative predictor of complete pathological response in HER2 positive locally advanced breast cancer
Monitoring therapy response in metastatic breast cancer using tumour markers CA15-3 and TPS
Therapeutic effect prediction based on biomarkers in the pleural effusion specimens of breast cancer patients
Outpatient catumaxomab therapy in metastatic breast cancer patients suffering from malignant effusions due to peritoneal or pleural
carcinomatosis: a single institution experience
Which is more beneficial as an initial therapy for the first distant metastasis of breast cancer: chemotherapy or endocrine therapy for
hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer patients?: A single-center study
The CTPET/MDST ratio: an introduction of a quantitative measure of effective palliative endocrine therapy in metastatic breast cancer
Therapeutic strategy for recurrent HER2-positive breast cancer patients
Locally advanced breast cancer in young female. The Egyptian National Cancer Institute experience.
Elderly women and breast cancer: characterization of treatment practices
Elderly metastatic breast cancer at diagnosis: a single institution experience
Elevated neutrophil to lymphocyte ratio predicts worse survival outcome after recurrence for patients with triple negative breast cancer
Compliance and persistence to palliative endocrine therapy in metastatic breast cancer
epidemiology and therapeutic management of metastatic breast cancer in Bulgaria: A retrospective cohort study
Current status of the management of advanced RH+/Her2- breast cancer in Morocco
Fulvestrant combined with capecitabine may be effective and well tolerated for patients with estrogen receptor-positive, HER2-negative
metastatic breast cancer.
Our treatment strategy for patients with hormone-receptor-positive, Her2-positive metastatic breast cancer
Retrospective study of everolimus with fulvestrant in postmenopausal women with hormone receptor-positive metastatic breast cancer
pretreated with aromatase inhibitors(AI's) and selective estrogen modifiers
Combination therapy peruzumab, trastuzumab and docetaxel for advanced or recurrent breast cancer patients in the late line
Experience with eribulin in the treatment of metastatic breast cancer in Tatarstan Republic clinical oncological dispensary
Inflammatory breast cancer – does dermal lymphatic invasion influence the outcome?
Basic clinical issues of inflammatory carcinoma of the breast
No palliative systemic antineoplastic therapy in patients with distant metastatic breast cancer: a blind spot in the perception of oncology?
National Clinical Breast Cancer Registry: views & approaches
The changes of platelet-lymphocyte ratio as a sensitive tumor marker to predict progression in metastatic breast cancer
Tumor marker (CA 15-3) monitoring failed to detect disease relapse and triggered unnecessary procedures – report of two cases
Paraneoplastic cerebellar degeneration and breast cancer
S84
Abstract list / The Breast 24 S3 (2015) S82–S85
Abstracts – Clinical Issues: Radiation Oncology
PO96
Characterisation of breast cancer brain metastases through a 21-year period – a study from the Swedish Association of Breast Oncologists
(SABO)
PO97
Brain metastases in HER2- positive breast cancer patients - a single institute experience
PO98 Is brain metastases location associated with prognosis in breast cancer patients?
PO99 Treatment outcomes of breast cancer brain metastases
PO100 IMRT-SIB for locally advanced inoperable breast cancer patients
PO101 Prognostic factors after gamma knife radiosurgery in breast cancer patients with brain metastases
PR102 Sternal recurrence in treated patients of advanced stage carcinoma breast - An emerging entity
Abstracts – Clinical Issues: Surgical Oncology
BP103
PO104
PO105
PO106
PO107
PO108
PO109
PO110
PR111
Electrochemotherapy in the treatment of cutaneous metastases from breast cancer: a multicenter cohort analysis
The surgical management of lung nodules in breast cancer patients
Success and failure of primary medical, non-operative management in patients who present with stage IV breast cancer
N2 lymph nodes post-primary chemotherapy may predict recurrence in locally advanced breast cancer
Surgical resection of the primary tumor is associated with increased long-term survival in patients with stage IV breast cancer
Novel and safe techniques in immediate breast reconstruction for locally advanced breast cancer particularly inflammatory breast cancer
The impact of locoregional treatment of primary metastatic breast cancer
Metastases of lobular breast carcinoma in the terminal ileum and ileocaecal valve
Surgical treatment of advanced breast cancer. Urgency of the problem
Abstracts – Clinical Issues: Supportive and Palliative Care
PO112
PR113
PO114
PO115
PO116
PO117
PR118
PR119
PR120
PR121
Efficacy of NEPA, the first combination antiemetic agent, in patients with breast cancer receiving anthracycline/cyclophosphamide (AC) or
non-AC chemotherapy
Comparative assessment of analgesic therapy in patients with breast cancer in the terminal stage
Using of hepatoprotectors in the drug treatment of patients with advanced breast cancer
The emotional toll of metastatic breast cancer on young women
The last quarter of a honeymoon – A wedding’s story
Can we make a portrait of women with inoperable locally advanced breast cancer? The experience of the Breast Unit of Southern
Switzerland (CSSI)
Comparison of integrative care expectations between breast cancer patients and breast oncology physicians in an ethnically diverse
population
Sensitizing Primary healthcare workers towards psychosocial issues of breast-cancer patients
Difficulties in providing palliative care in rural India (West Bengal) – experience of an NGO
Telephonic communication in palliative care for better management of terminal cancer patients in rural India– an NGO based approach
Abstracts – Clinical Issues: Other Topics
PO122
PR123
PR124
PR125
PR126
PR127
Sodium fluoride PET/CT: a superior imaging modality in evaluation of osseous metastatic disease
Patients’ own decision about becoming aware of recurrence earlier
Rumination and cancer disease: a cross-sectional study in a cohort of patients with breast and lung cancer
Some patterns of breast cancer epidemiology
Access to care for advanced breast cancer in middle-income country: example of Morocco
Changes of statistics of breast cancer in Ukraine during the period of 2003-2013
Abstracts – Basic and Translational Research
OR128 CTL and IgG response to tumor-associated antigens as predictive factors of therapeutic peptide vaccination for patients with metastatic
recurrent breast cancer
BP129 Insulin resistance (IR) and prognosis of metastatic breast cancer (MBC) patients
PO130 Clinical utility of the expression of HER3, HER4, PTEN and IGF1R in HER2-positive advanced or metastatic breast cancer
PO131 Heterogeneity in the expression of hormone receptors and HER2 between the primary breast cancer and pulmonary metastasis.
PO132 Apoptotic activities of recombinant cell surface receptor fas within tumor microenvironment of breast carcinoma
PO133 Differential expression of plasma membrane proteins in inflammatory breast cancer via stable isotope labeled amino acids in culture
(SILAC)
PO134 Analysis of primary breast cancer (BC) expression of programmed cell death 1 (PD-1) receptor and programmed death ligand 1 (PD-L1) to
determine associations with clinical characteristics and outcomes
PO135 At a glance the BRCAs epigenetic study in Padang, West Sumatera, Indonesia
PR136 Predictive value of mRNA expression of TUBIII gene in the treatment of locally advanced breast cancer
PR137 Contradictories in vitamin D supplementation on gene expression of microRNAs involving in breast carcinogenesis
PO138 P-cadherin: a candidate biomarker for axillary-based breast cancer decisions in clinical practice
PO139 Receptor activator of nuclear factor kappa B (RANK) expression in primary breast cancer correlates with recurrence free survival and
development of bone metastases in the I-SPY 1 trial (CALGB 150007/150012; ACRIN 6657)
Abstract list / The Breast 24 S3 (2013) S82–S85
S85
PO140 Changing in tumor biology of triple negative breast cancer between primary and metastatic lesions
PO141 Successful use of HER2 targeted agents in patients with heavily pretreated HER2-negative metastatic breast cancer presenting with
elevated serum levels of the HER2 extracellular domain and/or HER2 overexpressing circulating tumor cells
PO142 Evolution of the expression of circulating tumor cells (CTC) and CK-19 mRNA (CK19) as prognostic factors in heavily pretreated metastatic
breast cancer
PO143 Prognostic impact of circulating tumor cell clusters and apoptosis in metastatic breast cancer
PO144 Synergistic antitumor effects of crocin combined with hyperthermia on breast cancer cells
PO145 ICORG 13-01 ABC survey: are we meeting the needs of patients with advanced breast cancer (ABC) in Ireland? A nationwide survey
PR146 Locoregional recurrence by tumor biology in breast cancer patients after preoperative chemotherapy and breast conservation treatment
PR147 Intratumoral morphological heterogeneity of breast cancer and its implication in chemotherapy resistance
PR148 Androgen receptor (AR) expression as a promising index of the prediction of distant metastasis of triple negative breast cancer (TNBC)
PR149 Prognostic significance of Ki67 protein expression in metastatic breast cancer survival
PR150 Prognostic impact of 25-hydroxyvitamin D levels in Egyptian patients with breast cancer
PR151 Effects of phytoestrogen extracts isolated from elder flower on hormone production and receptor expression of trophoblast tumour cells
JEG-3 and BeWo, as well as MCF-7 breast cancer cells
PR152 Is NGS still efficient in finding new genes for breast cancer?
PR153 Vitamin D importance in the oncology consultation for the breast cancer’s patient
PR154 Evaluation of cardiotoxicity in breast cancer patients with human epidermal growth factor receptor-2 overexpression undergoing
trasuzumab treatment