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DEPARTMENT OF ONCOLOGY AND HEMATOLOGY

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DEPARTMENT OF ONCOLOGY AND HEMATOLOGY UNIVERSITY OF MODENA AND REGGIO EMILIA MODENA, ITALY I fattori prognostici del tumore della mammella: possibile un approccio ... – PowerPoint PPT presentation

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Title: DEPARTMENT OF ONCOLOGY AND HEMATOLOGY


1
DEPARTMENT 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
2
End points of cancer registry
  • Incidence
  • Mortality
  • Temporal trends in incidence and mortality
  • To allow for a rational planning of cancer
    control

3
Breast 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

4
Adjuvant Chemotherapy for Breast CancerBeyond
anatomic staging is it time to take the leap
into molecular era?Working group
5
Breast Cancer Registry and Molecular Subtypes
  • Prevention
  • Treatment
  • Follow up

6
BRCA 1 2
location tumor BRCA 1 17q21 breast,
ovary,prostate BRCA2 13q13 breast, male breast,
colon pancreas

7
BRCA 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


8
BRCA 1 2 Prophylaxis Healthy carriers
  • Chemoprevention
  • tamoxifen
  • droloxifen
  • raloxifen
  • AIs
  • Prophylactic mastectomy
  • Chemical castration
  • Prophylactic bilateral oophorectomy


9
Breast Cancer Registry and Molecular Subtypes
  • Prevention
  • Treatment
  • Follow up

10
BREAST 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
  • Predictive Markers
  • 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

11
EARLY 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)
12
GENERAL 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
13
Node 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
14
DEFINING THE TARGET IHC AND FISH
Abnormal 2
Abnormal 3
Normal 0
Normal 1
Normal
Normal
IHC Images by Kornstein, MD, Medical College of
Virginia
15
Distant DFS by HER-2 status in pT1N0M0 stage a
nationwide population-based study (852 patients)
Joensuu H et al. Clin Cancer Res, 2003
16
Disease-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
17
How 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)

18
HER2 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

19
Disease-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
20
HER 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
21
Molecular Portrait of Breast Cancers
Luminal B
Normal
HER-2
Basal-like
Luminal A
Sorlie T et al, PNAS 2001
22
Kaplan-Meier analysis of disease outcome in two
patient cohorts
S0rlie, Therese et al. (2003) Proc. Natl. Acad.
Sci. USA 100, 8418-8423
23
Molecular 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
24
Breast 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
25
Breast Cancer Registry and Molecular Subtypes
  • Prevention
  • Treatment
  • Follow up

26
Annual risk of recurrence by N
Saphner T, et al. J Clin Oncol 14 2738, 1996
27
Annual risk of recurrence by ER
Saphner T, et al. J Clin Oncol 14 2738, 1996
28
Breast 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
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