OUTLINE PAST PRESENTFUTURE BREAST CANCER INCIDENCE AND MORTALITY CURRENT STATE OF MEDICAL ONCOLOGY SECOND ANNUAL BREAST CANCER SYMPOSIUM

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OUTLINE CURRENT STATE OF MEDICAL ONCOLOGY

11, 2014 PAST PRESENTFUTURE -BRIEF HISTORICAL

(HER2+) -TRIPLE NEGATIVE (TNBC) -GENETICS

1 OUTLINE CURRENT STATE OF MEDICAL ONCOLOGY SECOND ANNUAL BREAST CANCER SYMPOSIUM October 11, 2014 SARA M GARRIDO, M.D., F.A.C.P Chief Medical Officer at AMS Miami, October 11, 2014 PAST PRESENTFUTURE -BRIEF HISTORICAL REVIEW -HORMONE RECEPTOR (HR+) -HER 2 DISEASE (HER2+) -TRIPLE NEGATIVE (TNBC) -GENETICS Timothy L. Grant, M.D., FAASM BREAST CANCER INCIDENCE AND MORTALITY 1

2 BREAST CANCER INCIDENCE BY RACE BREAST CANCER THE PAST 2

3 BREASTCANCER THE PAST BREAST CANCER -THE PRESENT EARLY ADJUVANT CHEMOTHERAPY 3

4 BREAST CANCER SUBTYPES BREAST CANCER SUBTYPES SUBTYPES Luminal A Luminal B Her2 Normal Basal like Nature Medicine 15, (2009) BREAST CANCER SUBTYPES BREAST CANCER SUBTYPES 4

PATHOLOGICAL/CLINICAL VARIABLES MORE AND MORE MOLECULAR TOOLS BREAST CANCER

5 BREAST CANCER CLASSIFICATION MULTIMODALITY THERAPY PATHOLOGICAL VARIABLES AND MOLECULAR SUBTYPES CONCORDANCE ~75% CLINICAL DECISIONS TODAY PATHOLOGICAL/CLINICAL VARIABLES MORE AND MORE MOLECULAR TOOLS BREAST CANCER THERAPY ESTROGEN RECEPTOR POSITIVE (ER+) AND/OR PROGESTERONE RECEPTOR + (PR+) BREAST CANCER 5

6 WHAT DO WE KNOW ABOUT ADJUVANT THERAPY FOR HR+ BREAST CANCER? 1) CHEMOTHERAPY : SOMETIMES 1) HORMONAL THERAPY: YES! BENEFIT OF COMBINATION CHEMOTHERAPY FOR LN + BREAST CANCER CHEMOTHERAPY METAANALYSIS 6

7 HORMONE + BREAST CANCER WHO DOESN T NEED CHEMOTHERAPY? PARADIGM SHIFT: FROM STAGE AND RISK-INFORMED PROCESS TO A TUMOR-BIOLOGY DRIVEN PROCESS 7

2001: CONSENSUS STATEMENT 2003: ONCOTYPE STARTED TO DEVELOP, NSABP-14: VALIDATION AS A

8 ONCOTYPE DX- RECURRENCE SCORE ONCOTYPE DX ONCOTYPE DX VALIDATION HR+/LN - ADJUVANT CHEMOTHERAPY WHO DOESN T NEED IT? 2001: CONSENSUS STATEMENT 2003: ONCOTYPE STARTED TO DEVELOP, NSABP-14: VALIDATION AS A PROGNOSTICATOR 2006: NSABP 20: VALIDATION AS PREDICTIVE : STANDARD OF CARE FOR LN-, HR+ EARLY BREAST CANCER 2013: VALIDATION IN LN POSITIVE DISEASE (1-3 + LNs) RxPONDER TRIAL 8

9 META-ANALYSIS /ONCOTYPE DX Timothy L. Grant, M.D., FAASM INFLUENCE OF THE RS TREATMENT DECISIONS FOR LN NEG, HR+ BREAST CANCER PATIENTS Timothy L. Grant, M.D., FAASM 9

10 RS CHEMO DECISION MAKING IN LN+ (1-3), HR+ PATIENTS RXPONDER TRIAL SWOG S1007 WHAT DO WE KNOW ABOUT ADJUVANT THERAPY FOR HR+ BREAST CANCER? 1) CHEMOTHERAPY : SOMETIMES 1) HORMONAL THERAPY: YES! 10

11 HORMONAL THERAPY HORMONAL THERAPY FIRST TARGETED THERAPY METAANALYSIS 11

12 BREAST CANCER BREAST CANCER HER 2+ HER 2 POSITIVE DISEASE AGGRESSIVE DISEASE ONE OF THE MOST TREATABLE /CURABLE ERB 2 ONCOGENE DRIVER STANDARDIZITON OF HER 2 TESTING IN PROGRESS TREATMENT OF MBC HER2+ - MILESTONE 12

13 HER 2 + BREAST CANCER- ADJUVANT THERAPY HER 2 + BREAST CANCER ANTI-HER2 DRUGS TRASTUZUMAB FOR HER 2 + BREAST CANCER Nature Reviews Molecular Cell Biology 7, (July 2006) 13

14 HER 2 + BREAST CANCER ADO TRASTUZUMAB EMTANSINE (TDM-1) MAGIC BULLET ADO TRASTUZUMAB EMTANSINE (TDM-1) T-DM1 / ASCO

15 PERTUZUMAB 15

16 METASTATIC BREAST CANCER HER ALGORITHM MBC HER2+ FUTURE TRIPLE NEGATIVE BREAST CANCER / BASAL LIKE 16

17 TRIPLE NEGATIVE / BASAL LIKE CONCORDANCE TRIPLE NEGATIVE BREAST CANCER TRIPLE NEGATIVE BREAST CANCER SURVIVAL TRIPLE NEGATIVE BREAST CANCER & BRCA MUTATIONS 17

18 SYNTHETIC LETHALITY: BRCA+ & SPORADIC BRCANESS METASTATICTRIPLE NEGATIVE BREAST CANER 18

19 BREAST CANCER THERAPY BREAST CANCER ADJUVANT ADJUVANT CHEMOTHERAPY ADJUVANT CHEMOTHERAPY 19

20 BREAST CANCER GENETICS BRCA+ - CANCER RISK TRIPLE NEGATIVE BREAST CANCER RISK 20

GUIDELINES FOR BOC GENETIC ASSESSMENT GUIDELINES FOR HBOCS

CANCER: MULTIPLE SUBTYPES /DIFFERENT PROGNOSIS AND

THE MOST USED TO MAKE THERAPEUTIC DECISIONS/ ~75%

21 GUIDELINES FOR BOC GENETIC ASSESSMENT GUIDELINES FOR HBOCS TESTING COMMERCIAL GENETIC PANELS CONCLUSIONS BREAST CANCER: MULTIPLE SUBTYPES /DIFFERENT PROGNOSIS AND THERAPEUTIC IMPLICATIONS CLINICOPATHOLOGIC CLASSIFICATION THE MOST USED TO MAKE THERAPEUTIC DECISIONS/ ~75% CONCORDANCE WITH MOLECULAR SUBTYPES CLASSIFICATION FUTURE:MOLECULAR SUBTYPES IS 21

HER 2 +: AGGRESSIVE DISEASE/EFFECTIVE TREATMENT ADVANCES: TRASTUZUMAB, PERTUZUMAB, TDM-1, LAPATINIB TNBC: AGGRESSIVE DISEASE, NO

22 CONCLUSIONS HR+ CONCLUSIONS PARADIGM SHIFT TO TUMOR-BIOLOGY DRIVEN PROCESS ADJUVANT CHEMOTHERAPY HAS DECREASED ~30% OPTIMAL DURATION OF HORMONAL THERAPY 10y? HER 2 +: AGGRESSIVE DISEASE/EFFECTIVE TREATMENT ADVANCES: TRASTUZUMAB, PERTUZUMAB, TDM-1, LAPATINIB TNBC: AGGRESSIVE DISEASE, NO SPECIFIC BIOLOGIC TREATMENT, POOR PROGNOSIS ROLE OF OVARIAN SUPPRESSION/ABLATION? GENETICS: A LOT NEW MUTATIONS, UNCLEAR IMPLICATIONS FOR PATIENTS AND DOCTORS OVERCOMING HORMONAL RESISTANCE IS AN EVOLVING AND PROMISING FIELD 22

Adjuvant Systemic Therapy in Early Stage Breast Cancer

Adjuvant Systemic Therapy in Early Stage Breast Cancer Julie R. Gralow, M.D. Director, Breast Medical Oncology Jill Bennett Endowed Professor of Breast Cancer Professor, Global Health University of Washington