Title: DEPARTMENT OF ONCOLOGY AND HEMATOLOGY
1DEPARTMENT OF ONCOLOGY AND HEMATOLOGY UNIVERSITY
OF MODENA AND REGGIO EMILIA MODENA, ITALY
I fattori prognostici del tumore della mammella
è possibile un approccio di popolazione ?
Prof. Pier Franco Conte
Reggio Emilia, 6 Aprile 2006
2End points of cancer registry
- Incidence
- Mortality
- Temporal trends in incidence and mortality
- To allow for a rational planning of cancer
control
3Breast Cancer in the last decade
- Increased Incidence
- lack of efficacy of primary prevention
- Decreased mortality
- Efficacy of secondary prevention (screening)
- More efficacious treatments
- In the adjuvant setting
- In the metastatic setting
4Adjuvant Chemotherapy for Breast CancerBeyond
anatomic staging is it time to take the leap
into molecular era?Working group
5Breast Cancer Registry and Molecular Subtypes
- Prevention
- Treatment
- Follow up
6BRCA 1 2
location tumor BRCA 1 17q21 breast,
ovary,prostate BRCA2 13q13 breast, male breast,
colon pancreas
7BRCA 1 2 Surveillance Healthy carriers
- Breast
- Breast self-exams
- Clinical breast exams
- Mammography
- New technologies ..(MRI)
-
- Ovary
- Clinical examinations
- Pelvic ultrasound
- Transvaginal ...ultrasound
- CA 125
-
8BRCA 1 2 Prophylaxis Healthy carriers
-
- Chemoprevention
- tamoxifen
- droloxifen
- raloxifen
- AIs
- Prophylactic mastectomy
-
- Chemical castration
- Prophylactic bilateral oophorectomy
-
9Breast Cancer Registry and Molecular Subtypes
- Prevention
- Treatment
- Follow up
10BREAST CANCER PROGNOSTIC and PREDICTIVE MARKERS
- Prognostic Markers
- Age/PS
- TNM
- Nuclear grade
- Hormone receptor status
- Proliferative status
- Her2 status
- Lymphovascular invasion
- Upa/PAI1
- Oncotype DX
- Gene expression profile
- Cyclins E and D1
- Cathepsin D
- p53
- Bcl-2
- VEGFr
- Hormone receptor status
- Her2 status
- Topoisomerase IIa
- Tau protein
- C-myc amplification
- ß-tubulin mutations
- Genetic polymorphism
- Gene espression profile
- Serum Biomarkers (CA 15.3, ECD,
- N-telopeptide)
- p53
11EARLY BC RISK CATEGORIES (ST. GALLEN 2005)
LOW RISK N - and ALL of the following features
pT 2cm
G1
Absence of peritumoral vascular invasion
HER2/neu gene neither overexpressed or amplified
Age gt 35 yrs
INTERMEDIATE N - and at least ONE of the following features
pT gt 2cm
G2-3
Peritumoral vascular invasion
HER2/neu gene overexpressed or amplified
Age lt 35 yrs
N (1-3 involved nodes) and
HER2/neu gene neither overexpressed or amplified
HIGH N (1-3 involved nodes) and
HER2/neu gene overexpressed or amplified
N (4 or more involved nodes)
12GENERAL TREATMENT RECOMMENDATIONS (ST.GALLEN
2005)
Risk Category Endocrine Responsive Doubtful Endocrine Resp Endocrine Non-Responsive
LOW ET ET -
INTERMEDIATE ET, or CT ? ET CT ? ET CT
HIGH CT ? ET CT ? ET CT
13Node BC Evolvement of Adjuvant Chemotherapy
Simulation
Relapse-free
100 80 60 40 20 0
Relapse risk/year TAC4 6,5 (-
32) AC T3 FEC2 AC1 10,0 (- 11)
CMF1 11,4 (- 24) Nil1 15,0
? 8 (-17)
TAC
0
2
4
6
8
10
Years
1 EBCTCG 2000 2 Levine, JCO 1998 FASG, JCO 2001
3 Henderson, JCO 2003 4 Martin, NEJM 2005
14DEFINING THE TARGET IHC AND FISH
Abnormal 2
Abnormal 3
Normal 0
Normal 1
Normal
Normal
IHC Images by Kornstein, MD, Medical College of
Virginia
15Distant DFS by HER-2 status in pT1N0M0 stage a
nationwide population-based study (852 patients)
Joensuu H et al. Clin Cancer Res, 2003
16Disease-Free Survival
AC?TH
87
85
AC?T
78
N Events AC?T 1679 261 AC?TH 1672 134
75
67
HR0.48, 2P3x10-12
Years From Randomization
B31/N9831
17How many breast cancers are HER2 ?
- 15-25
- (Slamon DJ, Science 1987)
- 10- 34
- (Molecular Oncology of Breast Cancer, JS
RossGN Hortobagyi,2005) - 20
- (NCI www.cancer.org 2005)
- 14.5
- (Modena Cancer Center, 2005)
18HER2 and Age
- Median age in trials
49 y - Median age (Omero project) 53 y
- Median age (Modena Cancer Center) 56 y
- Median age of Breast Cancer patients in
Modena Cancer Registry 62.3 yrs
19Disease-Free Survival
AC?TH
87
85
AC?T
78
71
N Events AC?T 1679 261 AC?TH 1672 134
75
67
HR0.48, 2P3x10-12
Years From Randomization
B31/N9831
20HER 2 TESTING CONCORDANCE BETWEEN LOCAL AND
CENTRAL LAB (N 9831 TRIAL)
Central HercepTest Score Central HercepTest Score Central HercepTest Score Central HercepTest Score Central HercepTest Score
0 0 1 2 3 Total
Local Her2 testing Local Her2 testing Local Her2 testing Local Her2 testing Local Her2 testing Local Her2 testing Local Her2 testing
IHC 8 9 9 12 81 110
FISH 1 1 1 0 7 9
Total 9 10 10 12 88 119
P Roche et al, JNCI 2002
21Molecular Portrait of Breast Cancers
Luminal B
Normal
HER-2
Basal-like
Luminal A
Sorlie T et al, PNAS 2001
22Kaplan-Meier analysis of disease outcome in two
patient cohorts
S0rlie, Therese et al. (2003) Proc. Natl. Acad.
Sci. USA 100, 8418-8423
23Molecular subtypes respond differently to PCT
- pCR rate after preoperative anthra-taxanes
combination
Basal like 45
Her2 45
Luminal 6
Normal-like 0
Rouzier et al, Clin Cancer Res 2005
24Breast cancer heterogeneity results of
gene-expression profile studies
Breast cancer type IHC surrogates pts
Basal-like ER- PR- HER2- HER1 20
HER2 HER2 ER- PR- 7
Luminal A ER or PR HER2- 51
Luminal B ER or PR HER2 16
Carey ASCO 2005
25Breast Cancer Registry and Molecular Subtypes
- Prevention
- Treatment
- Follow up
26Annual risk of recurrence by N
Saphner T, et al. J Clin Oncol 14 2738, 1996
27Annual risk of recurrence by ER
Saphner T, et al. J Clin Oncol 14 2738, 1996
28Breast Cancer Registry and Molecular Subtypes
- Molecular subtypes of breast cancer
- - require different diagnostic procedures
- - may have different risk/benefit ratio for
preventive interventions - - respond differently to treatments
- - have different annual risk of relapse
- A population-based registry of the molecular
subtypes of breast cancer would allow a more
rational planning of resource allocation