Download Updates on Breast Cancer

Updates on Breast Cancer
Ingrid Lizarraga, MBBS
April 19, 2017
Family Practice Refresher Course
No disclosures
Breast Cancer in 2017
• Breast cancer by the numbers
• Diagnosis and work up
• Biology of breast cancer
• Local therapy of breast cancer
• Systemic treatment
• Survivorship
Cancer Statistics 2017: American Cancer
Society
Incidence of breast cancer in Iowa
Source: www.cdc.gov
Breast cancer survival
The patient
• 53 yo female with a 2 week history of a palpable R breast lump
• G2P2
• Prior h/o breast cysts
• Maternal aunt with premenopausal breast cancer
Physical exam find a poorly circumscribed 2 cm firm mass in upper outer
quadrant, no skin changes, no nipple discharge or inversion, no palpable lymph
nodes
Mammogram
Focused breast US did not identify any abnormalities
In a patient with a palpable breast mass and
negative mammogram and US, the next
appropriate step is:
1)Reassurance
2)Repeat clinical exam in 2-3 months
3)MRI
4)Palpation guided needle biopsy
5)Excisional biopsy
ACR recommendation on the palpable breast
mass
• Over 30 start with a mammogram (to help characterize palpable
finding and identify other pathology ( eg calcs associated with mass
or other abnormalities)
• Breast US, regardless if mammo is nl
• Palpation guided core needle biopsy if no imaging correlate and
suspicious mass on palpation
New technology: tomosynthesis
• 3D mammography
• Improved detection of cancers in dense breasts
• Decreased call backs for more images
A word on breast cancer diagnosis
Breast practice:
• Breast cancer should be diagnosed by core needle biopsy, not
excisional biopsy where possible
• Lower cost, less invasive
• Allows for better preoperative planning and evaluation
Endorsed by American College of Surgeons and American Society of
Breast Surgeons; National QI measure of the Commission on Cancer
Palpation guided core needle biopsy results
• Invasive ductal carcinoma, Grade 3
• High grade ductal carcinoma in situ
• ER negative
• PR negative
• HER2 negative
Biology of breast cancer
Breast cancer – not just 1 disease anymore!
Subtypes:
Luminal A – usually strongly ER/PR+,
low grade
Luminal B - ER+/PR-, HER2+/ER+/PR+
Basal type - ER/PR/HER2-, high grade
HER2 enriched - HER2+, ER/PRHowever there is overlap in receptor
expression between groups!
Gene expression patterns of 85 experimental samples
analyzed by hierarchical clustering using the 476 cDNA
intrinsic clone set.
Therese Sørlie et al. PNAS 2001;98:10869-10874
Prognosis and subtype
Overall and relapse-free survival analysis of the 49 breast cancer patients, uniformly treated in
a prospective study, based on gene expression classification.
Breast cancer therapy
SURGERY FOR BREAST CANCER: LUMPECTOMY VS MASTECTOMY
Disease-free Survival (Panel A), Distant-Disease–free Survival (Panel B), and Overall Survival (Panel C) among 589 Women Treated
with Total Mastectomy, 634 Treated with Lumpectomy Alone, and 628 Treated with Lumpectomy plus Irradiation.
Fisher B et al. N Engl J Med 2002;347:1233-1241.
Lumpectomy
• Purpose is to remove all malignant tissue while maintaining normal
appearance of the breast.
Lumpectomy
Methods of localization
• Palpation guided
• Ultrasound guided
• Wire localized
• Radioactive seed/ magnetic localized
Oncoplastic lumpectomy
• Useful technique to preserve breast appearance when
removing large tumors
• Often requires plastic surgeon to complete
• Usually requires surgery on the other breast to ensure symmetry
Breast radiation
Decreases risk of local recurrence from 26% to 7% at 5 yrs.
Whole breast radiation
Partial breast radiation
• Catheter based
• Standard (6 weeks)
• Hypofractionated (3 weeks)
• Intraoperative radiation
Lumpectomy - Is radiation always needed?
Lumpectomy Plus Tamoxifen With or Without Irradiation in Women
Age 70 Years or Older With Early Breast Cancer: Long-Term Follow-Up
of CALGB 9343
Hughes et al, JCO 2013
Mastectomy
• Removal of the entire
breast
• Radiation only needed if
advanced disease
Breast reconstruction
• Purpose is to recreate a normal appearing breast mound
• May require a contralateral procedure for symmetry
• Nipple can be reconstructed or tattooed on
• Types:
• Immediate/ delayed
• Autologous /implant reconstruction
Women’s health and Cancer
ACT (janet's law)
Oct 21, 1998
Implant reconstruction
• 80% of all breast reconstructions in US
• Saline /silicone
Depending on amount of skin removed
and planned size of reconstructed
breast, reconstruction may require
expander placement.
Autologous reconstruction
1. Transverse abdominis muscle flap (TRAM)
2. Deep inferior epigastric perforator
flap (DIEP)
3. Latissimus dorsi flap
Breast reconstruction in the United states
Fig. 1 . Immediate breast reconstruction rate and reconstructive method in
the United States from 1998 to 2008.
Alboroz et al.Plast Reconstr Surg. 2013
Adjusted receipt of reconstruction for each state in the United States, using final logistic model adjusted for all covariates
except for density of plastic surgeons and county-level income.
Reshma Jagsi et al. JCO 2014;32:919-926
©2014 by American Society of Clinical Oncology
Mastectomy and immediate reconstruction:
Skin sparing mastectomy
Delayed flap reconstruction
Immediate flap reconstruction
Nipple sparing mastectomy – improvement in
cosmetic results
Before
After
Surgery for breast cancer:
Lumpectomy vs mastectomy
• Tumors 5 cm or smaller
• No contraindication for radiation
• Favorable breast/tumor ratio
• Large tumors
• Diffuse tumors
(multifocal/multicentric)
• Small breasts
• Tumors involving the nipple
• Inflammatory breast cancer
• Male breast cancer
• High risk mutation
• Patient preference
There is no survival advantage to mastectomy, even in high risk patients!
Mastectomy trends
Fig. 1
Overall national mastectomy rate (2000–2008)
Fig. 2
Mastectomy rates by age at diagnosis (2000–2008)
Mahmood, Ann Surg Oncol (2013)
Rising rate of contralateral prophylactic
mastectomy for unilateral breast cancer
Annual hazard rates for contralateral breast cancer (CBC)
over time and across age from 1975 to 2005
after a first breast cancer
Nichols et al, JCO 2010
American Society of Breast Surgeons Contralateral
Prophylactic Mastectomy (CPM) Consensus
Statement
Aug. 3, 2016
“The consensus group agreed that CPM should be discouraged for an
average-risk woman with unilateral breast cancer. However, patient’s
values, goals and preferences should be included to optimize shared
decision making when discussing CPM. The final decision whether or
not to proceed with a CPM is a result of the balance between benefits
and risks of CPM and patient preference.”
Axillary lymph node staging
• Breast cancer spreads
through blood and
lymphatic channels
• Lymph node status is
used in staging
Axillary dissection
• Removal of the axillary lymph nodes between the
axillary vein above, the pectoralis minor muscle
medially and the breast below
• 10-20 lymph nodes
• Traditionally part of
radical and modified
radical mastectomy
Potential adverse effects
• Lymphedema (progressive swelling of the arm – 10-20%
• Injury to nerves supplying the muscles of the shoulder
and chest
• Permanent restriction of
shoulder ROM/ function
Sentinel lymph node biopsy
• Developed in 1994
• Uses blue dye/
radioactive colloid to
identify the “sentinel
node”
• Proven to have 97%
accuracy in multicenter
trial in early 2000s
• 1-5 lymph nodes
removed
• Risk of lymphedema 5%
Sentinel lymph node biopsy vs axillary dissection
• Early stage breast cancer
• No clinical evidence of
cancer in lymph nodes
• Known cancer in the lymph
nodes (historically always)
BUT (new and exciting)! :
• Not in patients with 1-2+
nodes and breast conservation
• Not in patients with
previously positive lymph
nodes that have become
negative after chemotherapy
Systemic therapy for breast
cancer
Individualized medicine
• Anti-estrogen therapy
• Chemotherapy
• Immunotherapy
Antiestrogen therapy
• 40% risk reduction in risk of death for ER+ patients; 10 yrs vs 5yrs
• Tamoxifen (premenopausal), aromatase inhibitors (post menopausal)
Figure 5. Effects of about 5 years of tamoxifen on the 15-year probabilities of recurrence and
of breast cancer mortality, for ER-positive disease.
EBCTG, Lancet 2011
Chemotherapy
• 30 % risk reduction in
death
• Any triple negative or
HER2+ patient with
tumor >5mm should be
considered for
chemotherapy
• Adriamycin/Cytoxan and
Taxol standard course
Polychemotherapy versus not, by entry age <50 or 50–69 years:
15-year probabilities of recurrence and of breast cancer mortality
The Lancet 2005 365, 1687-1717DOI: (10.1016/S0140-6736(05)66544-0)
Who needs chemotherapy?
Individualized risk assessment
Genomic tumor testing to predict
benefit of chemotherapy in ER
positive patients
• Oncotype
• Mammaprint
Tool often used to decide
chemotherapy or not for node
negative ER+ breast cancer,
sometimes node positive as well
HER 2 positive breast cancer
• 25 % of breast cancers
• Poor prognosis before
targeted therapy developed
•
•
•
•
Traztuzamab
Pertuzumab
TDM 1
Capecitabine
So now what for our patient?
53 yo female with 2cm triple negative L breast cancer
Multidisciplinary tumor board discussion
Standard of care for breast cancer management*
• Oncologic surgery
• Medical Oncology
• Radiation oncology
• Radiology
• Pathology
• Genetics
• Nurse navigation
*Required for breast center accreditation
Prior treatment algorithm: operable breast
cancer
Surgery:
mastectomy or lumpectomy
Chemotherapy if needed
Radiation therapy
Endocrine therapy
If positive lymph nodes, remove all
Modern treatment algorithm
Operable breast cancer
Positive lymph nodes, large
tumor, HER2 positive cancer
Surgery first
Chemotherapy first
Chemotherapy if needed
Radiation therapy
Antiestrogen therapy if ER+
Surgery
Response to chemotherapy used to inform:
Need for radiation
Extent of lymph node surgery
Type and duration of antiestrogen therapy
prognosis
Tumor board recommendations
• Breast MRI for breast density
• Genetic testing
Who should get genetic testing?
National Comprehensive Cancer Network (NCCN) guidelines
• Known family history of mutation
• Male breast cancer
• Personal h/o breast cancer and:
• Pancreatic cancer or prostate cancer < 50y
with ≥ 2 relatives with
breast/ovarian/pancreatic cancer
•
•
•
•
•
•
•
Age <46yr
Bilateral breast cancer
Age <60 and triple negative breast cancer
Dx < 50y with 1 or more relatives with BC/OC
Dx any age with 2 or more relatives with BC/OC
Dx any age with 1 or more relative dx <50yrs
Dx any age with 2 or more relative with
pancreatic/prostate
• Dx any age with 1 or more relative with ovarian
Ca
• Personal history of ovarian cancer
• Family history only
• 1st/2nd degree relative meeting any above criteria
• Third degree relative with breast/ovarian with ≥
2 close relatives with breast/ovarian (at least 1
under 50yrs)
Breast MRI
L breast core needle biopsy showed grade 3 IDC, ER/PR/HER2 negative
L axillary lymph node core needle biopsy showed metastatic adenocarcinoma
BRCA testing results:
Positive for BRCA 1 deleterious
Mutation
3%/ year risk of contralateral
Breast cancer
Treatment recommendations
• Neoadjuvant chemotherapy
• Bilateral mastectomy with immediate implant mastectomy
• Prophylactic oophorectomy
• Final pathology showed pathological complete response in both
breast and sentinel lymph node.
• No axillary dissection done
• No post mastectomy radiation
Survivorship – what happens
now?
From Cancer Patient to Cancer Survivor: Lost
in Transition
• Institute of Medicine report published in 2005
• A committee was established at the IOM of the National Academies
to examine issues faced by cancer survivors and to make
recommendations to improve their health care and quality of life.
• Three goals of the report:
1. Raise awareness of the medical, functional, and psychosocial consequences
of cancer and its treatment.
2. Define quality health care for cancer survivors and identify strategies to
achieve it.
3. Improve the quality of life of cancer survivors through policies to ensure
their access to psychosocial services, fair employment practices, and health
insurance.
Survivorship
“Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle,
monitor for post treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine
Therapy…..
Recommendations on surveillance for breast cancer recurrence, screening for second
primary cancers, assessment and management of physical and psychosocial long-term and late effects of
breast cancer and its treatment, health promotion, and care coordination/practice implications are made.
Guidelines
•
•
•
•
•
F/u q 3-6 months until 2 years, then annual
Annual mammography, but no routine labs
Monitor compliance with antiestrogen therapy
Update family history and refer for genetic testing as appropriate
Promote healthy behavior
• Weight control – obesity associated with increase risk of recurrence
• Smoking cessation – higher risk of complications from breast radiation
• Monitor bone health
• postmenopausal breast cancer survivors need a baseline DEXA scan + repeat DEXA
scans every 2 y for women taking an aromatase inhibitor, premenopausal women
taking tamoxifen and/or a GnRH agonist, and women who have chemotherapyinduced premature menopause
Guidelines
Monitor for sequelae of treatment:
• Lymphedema
• Neuropathy – after chemotherapy most commonly
• Cardiac disease – from chemotherapy (adriamycin) and radiation
• Shoulder morbidity
• Cognitive impairment – ‘chemobrain’
• Depression, anxiety
• Body image issues
From Cancer Patient to Cancer Survivor: Lost
in Transition
IOM report goal : Define quality health care for cancer survivors and
identify strategies to achieve it
• Strategy recommendation: Patients completing primary treatment should be
provided with a comprehensive care summary and follow-up plan that is
clearly and effectively explained, coined the “Survivorship Care Plan”.
IOM: Survivorship Care Plan
• Summarize critical information needed for the survivor’s long-term
care:
• Cancer type, treatments received, and their potential consequences;
• Specific information about the timing and content of recommended followup;
• Recommendations regarding preventative practices and how to maintain
health and well-being;
• Information on legal protections regarding employment and access to health
insurance;
• The availability of psychosocial services in the community
Upcoming advances
• Molecular testing to dictate kind of chemotherapy
• Better risk assessment
• DCIS – to treat or not to treat
• Tailoring extent of surgery to biological response to treatment
• Durable survival with stage 4 disease
Thank you, and questions?