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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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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


Adjuvant Chemotherapy for Breast CancerBeyond anatomic staging: is it time to take the leap into molecular era?Working group


Breast cancer registry and molecular subtypes
Breast Cancer Registry and Molecular Subtypes

  • Prevention

  • Treatment

  • Follow up


BRCA 1 & 2

location tumor

BRCA 1 17q21 breast, ovary,prostate

BRCA2 13q13 breast, male breast, colon

pancreas


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


BRCA 1 & 2 Prophylaxis Healthy carriers

  • Chemoprevention:

  • tamoxifen

  • droloxifen

  • raloxifen

  • AIs

  • Prophylactic mastectomy

  • Chemical castration

  • Prophylactic bilateral oophorectomy


Breast cancer registry and molecular subtypes1
Breast Cancer Registry and Molecular Subtypes

  • Prevention

  • Treatment

  • Follow up


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




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


Disease-Free Survival population-based study (852 patients)

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+ ? population-based study (852 patients)

  • 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 population-based study (852 patients)

  • 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


Disease-Free Survival population-based study (852 patients)

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


Her 2 testing concordance between local and central lab n 9831 trial
HER 2 TESTING: CONCORDANCE BETWEEN LOCAL AND CENTRAL LAB population-based study (852 patients)(N 9831 TRIAL)

P Roche et al, JNCI 2002


Molecular portrait of breast cancers
Molecular Portrait of Breast Cancers population-based study (852 patients)

“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 population-based study (852 patients) 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 population-based study (852 patients)

pCR rate after preoperative anthra-taxanes combination

Rouzier et al, Clin Cancer Res 2005


Breast cancer heterogeneity results of gene expression profile studies
Breast cancer heterogeneity: population-based study (852 patients)results of gene-expression profile studies

Carey ASCO 2005


Breast cancer registry and molecular subtypes2
Breast Cancer Registry and Molecular Subtypes population-based study (852 patients)

  • Prevention

  • Treatment

  • Follow up


Annual risk of recurrence by n
Annual risk of recurrence by N population-based study (852 patients)

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


Annual risk of recurrence by er
Annual risk of recurrence by ER population-based study (852 patients)

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


Breast cancer registry and molecular subtypes3
Breast Cancer Registry and Molecular Subtypes population-based study (852 patients)

  • 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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