Download 2013 - Breast Cancer Research Centre WA

Breast cancer
Prof Arlene Chan
Medical Oncologist
Director Breast Clinical Trials Unit, Mount Hospital
Vice-Chair Breast Cancer Research Centre - WA
Breast cancer
Incidence of Breast Cancer by Stage
at Diagnosis (Europe 2005)
Stage
Number
% of Total
Stage I
70,270
38.1%
Stage II
85,140
46.3%
Stage III
17,130
9.3%
Stage IV
11,530
6.3%
Total
184,070
100%
Metastatic breast cancer:
improved survival over time
1.0
Cumulative survival
0.8
0.6
1995–2000
1990–1994
0.4
1985–1989
0.2
1980–1984
1974–1979
0.0
0
12
24
36
Months
48
60
How do we approach breast
cancer management to improve
outcome?
Research
Genetics
SYSTEMIC
treatment
(Drugs)
Diagnosis
LOCO-REGIONAL
treatment
(Surgery &
Radiation therapy
Improve outcome
in patients with
breast cancer
Risk factors
◊ Estrogen exposure:
» Physiological, Exogenous
◊ Growth factors
» Obesity, Alcohol
◊ Pre-cancerous breast conditions
◊ Chest irradiation – ‘huge’ doses
◊ Breast cancer-susceptible genes*
Diagnosis
◊ EBC (stage 1-3)
» Earlier diagnosis
translates into higher
chance of cure
» Once diagnosed, plan
best surgery ±
reconstruction ±
radiation therapy
» Discuss relapse risk
» Systemic treatment
◊ MBC (stage 4)
◊ Earlier diagnosis does
not translate into higher
rate of response or
survival
◊ Tissue diagnosis*** for
type of BrC
◊ Assess extent of BrC
◊ Assess fitness
◊ Give best therapy based
on evidence-based
research
Systemic therapy: Principles
• Breast cancer is a heterogeneous* disease
-> Different sub-types which behave differently:
• Different growth rates
• Responds to treatment differently (drugs /
radiation therapy)
• Although may “prefer” certain sites in body, this
does not have major effect on management
* Dissimilar; possessing different or opposing characteristics in the same
individual
Basal-like
HER-2
“Normal”
Luminal B
Luminal A
Sørlie et al. Proc Natl Acad Sci USA. 2001;98:10869-10874.
• Metastatic disease is generally considered
“incurable” but
• Very treatable
• Many options available – need to use in correct
order
• Choice depends on:
• Sub-type of breast cancer
• Where and how much metastatic cancer
• Underlying fitness of patient
• Any previous treatment given
Growth factor
Estrogen
EGFR / Her2
Her3/Her2
IGFR
EGFR / HER2
Plasma
membran
e
P
P
P
P
P
P
P
PI3-K
Cell
survival
Akt
P
SOS
RAS
RAF
P
MEK
P
ER
p90RSK
Cytoplas
m
P
Nucleus
P
P
P ER
ER
ERE
p160
CBP
P
MAPK
Basal
transcription
machinery
P
Cell
growth
ER target gene transcription
Adapted from Johnston S. Clin Cancer Res. 2005;11:889S-899S.
Types of systemic therapy
◊ Endocrine therapy
» Tamoxifen
» Aromatase inhibitors: Letrozole, Anastrozole,
Exemestane
» Ovary suppression
◊ Chemotherapy
◊ Biologic therapy
Biological
drug
Endocrine
drug
Chemotherapy
drug
Supportive
tissues cells
VEGF
TGF
EGFR
ER
HER2
GF-R
VEGF-R
Cell
membrane
Nuclear
membrane
Gene transcription
Cell growth
and proliferation
Inhibition of apoptosis
Increased cell mobility
Tumor growth
Resistance to chemotherapy
Metastasis
Inside cell
Signaling cascade
Breast cancer Research
Principles
Tumour behavior
Concept
Understand tumour biology
Understand patient needs?
Desig
n
Execution
Scientific design:
Patients in study must be “the same”
Must show it’s not a chance finding
Primary aim to
be achieved
Source
funding
Timely
recruitment
Many centres
required
Regulatory aspects
Analyse data
Collect all data (years)
Publish
Constant check of data
U.S. FDA approval in MBC
Trastuzumab
2000
Nab paclitaxel
Docetaxel Capecitabine
Methotrexate
1996
1998
Gemcitabine 2005
1971
2004
Lapatinib
Doxorubicin Paclitaxel
Cyclophosphamide
2007
1974
1994
1959
Bevacizumab
2008
1955
1965
1975
1985
1995
2005
2015
Conclusions
◊ Breast cancer has many facets
Education of:
» Risks – Detection – Differing behaviour
» Local & Systemic treatment options
» Early vs Metastatic disease
•Patients
•Community/Gov
» Short & Long term consequences of treatment
» Addressing non-medical needs
◊ Multidisciplinary approach
◊ Best outcome requires application of
scientifically-proven treatments
•GP
•Allied health
•Specialists