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DEPARTMENT OF ONCOLOGY AND HEMATOLOGY UNIVERSITY OF MODENA AND REGGIO EMILIA MODENA, ITALY

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

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  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. 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

  11. EARLY BC: RISK CATEGORIES (ST. GALLEN 2005)

  12. GENERAL TREATMENT RECOMMENDATIONS(ST.GALLEN 2005)

  13. 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

  14. 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

  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 % % NEvents ACT 1679 261 ACTH 1672 134 75 % 67 % HR=0.48, 2P=3x10-12 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 Ross&GN 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% % NEvents ACT 1679 261 ACTH 1672 134 75 % 67 % HR=0.48, 2P=3x10-12 Years From Randomization B31/N9831

  20. HER 2 TESTING: CONCORDANCE BETWEEN LOCAL AND CENTRAL LAB (N 9831 TRIAL) P Roche et al, JNCI 2002

  21. Molecular Portrait of Breast Cancers “Normal” Luminal B 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 Rouzier et al, Clin Cancer Res 2005

  24. Breast cancer heterogeneity: results of gene-expression profile studies 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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