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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. End points of cancer registry. Incidence

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slide1
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

end points of cancer registry
End points of cancer registry
  • Incidence
  • Mortality
  • Temporal trends in incidence and mortality

To allow for a rational planning of cancer control

breast cancer in the last decade
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
slide4
Adjuvant Chemotherapy for Breast CancerBeyond anatomic staging: is it time to take the leap into molecular era?Working group
slide6
BRCA 1 & 2

location tumor

BRCA 1 17q21 breast, ovary,prostate

BRCA2 13q13 breast, male breast, colon

pancreas

slide7
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
slide8
BRCA 1 & 2 Prophylaxis Healthy carriers
  • Chemoprevention:
  • tamoxifen
  • droloxifen
  • raloxifen
  • AIs
  • Prophylactic mastectomy
  • Chemical castration
  • Prophylactic bilateral oophorectomy
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

BREAST CANCER: PROGNOSTIC and PREDICTIVE MARKERS
  • Hormone receptor status
  • Her2 status
  • Topoisomerase IIα
  • Tau protein
  • C-myc amplification
  • β-tubulin mutations
  • Genetic polymorphism
  • Gene espression profile
  • Serum Biomarkers (CA 15.3, ECD,
  • N-telopeptide)
  • p53
slide13
AC - T/FEC

AC

CMF

Nil

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

defining the target ihc and fish
Abnormal low

Abnormal high

amplification

amplification

DEFINING THE TARGETIHC AND FISH

Normal 0

Normal 1+

Abnormal 2+

Abnormal 3+

Normal

Normal

IHC Images by Kornstein, MD, Medical College of Virginia

distant dfs by her 2 status in pt1n0m0 stage a nationwide population based study 852 patients
Distant DFS by HER-2 status in pT1N0M0 stage: a nationwide population-based study (852 patients)

Joensuu H et al.: Clin Cancer Res, 2003

slide16
Disease-Free Survival

ACTH

87%

85%

ACT

78 %

%

NEvents

ACT 1679 261

ACTH 1672 134

75 %

67 %

HR=0.48, 2P=3x10-12

Years From Randomization

B31/N9831

how many breast cancers are her2
How many breast cancers are HER2+ ?
  • 15-25%

(Slamon DJ, Science 1987)

  • 10- 34%

(Molecular Oncology of Breast Cancer, JS Ross&GN Hortobagyi,2005)

  • ~ 20 %

(NCI; www.cancer.org 2005)

  • 14.5 %

(Modena Cancer Center, 2005)

her2 and age
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

slide19
Disease-Free Survival

ACTH

87%

85%

ACT

78 %

71%

%

NEvents

ACT 1679 261

ACTH 1672 134

75 %

67 %

HR=0.48, 2P=3x10-12

Years From Randomization

B31/N9831

molecular portrait of breast cancers
Molecular Portrait of Breast Cancers

“Normal”

Luminal B

HER-2

Basal-like

Luminal A

Sorlie T et al, PNAS 2001

kaplan meier analysis of disease outcome in two patient cohorts
Kaplan-Meier analysis of disease outcome in two patient cohorts

S0rlie, Therese et al.

(2003) Proc. Natl. Acad. Sci. USA 100, 8418-8423

molecular subtypes respond differently to pct
Molecular subtypes respond differently to PCT

pCR rate after preoperative anthra-taxanes combination

Rouzier et al, Clin Cancer Res 2005

annual risk of recurrence by n
Annual risk of recurrence by N

Saphner T, et al. J Clin Oncol 14: 2738, 1996

annual risk of recurrence by er
Annual risk of recurrence by ER

Saphner T, et al. J Clin Oncol 14: 2738, 1996

breast cancer registry and molecular subtypes3
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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