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1
CURRENT STATE OF MEDICAL ONCOLOGY
SECOND ANNUAL
BREAST CANCER SYMPOSIUMOctober 11, 2014
SARA M GARRIDO, M.D., F.A.C.P
Chief Medical Officer at AMS
Miami, October 11, 2014
Timothy L. Grant, M.D., FAASM
OUTLINE
PAST ����PRESENT����FUTURE
-BRIEF HISTORICAL REVIEW
-HORMONE RECEPTOR (HR+)
-HER 2 DISEASE (HER2+)
-TRIPLE NEGATIVE (TNBC)
-GENETICS
BREAST CANCER INCIDENCE
AND MORTALITY
2
BREAST CANCER INCIDENCE
BY RACE 2006-2010
BREAST CANCER – THE PAST
3
BREAST CANCER – THE PASTBREAST CANCER -THE PRESENT
EARLY ADJUVANT CHEMOTHERAPY EARLY ADJUVANT CHEMOTHERAPY
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BREAST CANCER SUBTYPES BREAST CANCER SUBTYPES
SUBTYPES
Luminal A
Luminal B
Her2
Normal
Basal like
___________________
Nature Medicine
15, 842-844 (2009)
BREAST CANCER SUBTYPES BREAST CANCER SUBTYPES
5
BREAST CANCER CLASSIFICATION
PATHOLOGICAL VARIABLES AND MOLECULAR SUBTYPES CONCORDANCE ~75%
CLINICAL DECISIONS TODAY ����
PATHOLOGICAL/CLINICAL VARIABLES…MORE AND MORE MOLECULAR TOOLS
MULTIMODALITY
THERAPY
BREAST CANCER THERAPY
ESTROGEN RECEPTOR POSITIVE (ER+)
AND/OR
PROGESTERONE RECEPTOR + (PR+)
BREAST CANCER
6
WHAT DO WE KNOW ABOUT
ADJUVANT THERAPY FOR HR+
BREAST CANCER?
1) CHEMOTHERAPY : SOMETIMES
1) HORMONAL THERAPY: YES!
CHEMOTHERAPY METAANALYSIS
BENEFIT OF COMBINATION
CHEMOTHERAPY FOR LN +
BREAST CANCER
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HORMONE + BREAST CANCER
FROM STAGE AND RISK-INFORMED PROCESS TO A TUMOR-BIOLOGY
DRIVEN PROCESS
FROM STAGE AND RISK-INFORMED PROCESS TO A TUMOR-BIOLOGY
DRIVEN PROCESS
WHO DOESN’T NEED CHEMOTHERAPY?WHO DOESN’T NEED CHEMOTHERAPY?
PARADIGM SHIFT:
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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
2006����2014: STANDARD OF CARE FOR LN-, HR+ EARLY BREAST CANCER
2013: VALIDATION IN LN POSITIVE DISEASE (1-3 + LNs) ���� RxPONDER TRIAL
9
Timothy L. Grant, M.D., FAASM
META-ANALYSIS /ONCOTYPE
DX
INFLUENCE OF THE RS� TREATMENT DECISIONS FOR LN NEG, HR+ BREAST
CANCER PATIENTS
Timothy L. Grant, M.D., FAASM
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!
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HORMONAL THERAPY FIRST TARGETED THERAPY
METAANALYSIS
HORMONAL THERAPY
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BREAST CANCER
HER 2 POSITIVE DISEASE
AGGRESSIVE DISEASE
ONE OF THE MOST TREATABLE /CURABLE
ERB 2 ONCOGENE DRIVER
STANDARDIZITON OF HER 2 TESTING IN PROGRESS
BREAST CANCER –
HER 2+
TREATMENT OF MBC
HER2+ - MILESTONE
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HER 2 + BREAST CANCER-
ADJUVANT THERAPY
HER 2 + BREAST CANCER
ANTI-HER2 DRUGS
Nature Reviews Molecular Cell Biology 7, 505-516 (July 2006)
TRASTUZUMAB FOR HER 2 + BREAST CANCER
14
HER 2 + BREAST CANCER ADO TRASTUZUMAB EMTANSINE(TDM-1) – “MAGIC BULLET”
ADO TRASTUZUMAB
EMTANSINE (TDM-1)T-DM1 / ASCO 2012
15
PERTUZUMAB
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METASTATIC BREAST
CANCER – HER 2+ 2013-2014 ALGORITHM
MBC HER2+ FUTURE TRIPLE NEGATIVE BREAST
CANCER / BASAL LIKE
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TRIPLE NEGATIVE / BASAL
LIKE CONCORDANCE TRIPLE NEGATIVE BREAST CANCER
TRIPLE NEGATIVE BREAST
CANCER SURVIVAL
TRIPLE NEGATIVE BREAST
CANCER & BRCA MUTATIONS
18
SYNTHETIC LETHALITY:
BRCA+ & SPORADIC “BRCANESS”
METASTATIC TRIPLE
NEGATIVE BREAST CANER
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BREAST CANCER THERAPY BREAST CANCER ADJUVANT
ADJUVANT CHEMOTHERAPY ADJUVANT CHEMOTHERAPY
20
BREAST CANCER GENETICS
BRCA+ - CANCER RISKTRIPLE NEGATIVE BREAST
CANCER RISK
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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
22
CONCLUSIONS HR+
PARADIGM SHIFT TO TUMOR-BIOLOGY DRIVEN PROCESS
ADJUVANT CHEMOTHERAPY HAS DECREASED ~30%
OPTIMAL DURATION OF HORMONAL THERAPY 10y?
ROLE OF OVARIAN SUPPRESSION/ABLATION?
OVERCOMING HORMONAL RESISTANCE IS AN EVOLVING AND PROMISING FIELD
CONCLUSIONS
HER 2 +: AGGRESSIVE DISEASE/EFFECTIVE TREATMENT
ADVANCES: TRASTUZUMAB, PERTUZUMAB, TDM-1, LAPATINIB
TNBC: AGGRESSIVE DISEASE, NO SPECIFIC BIOLOGIC TREATMENT, POOR PROGNOSIS
GENETICS: A LOT NEW MUTATIONS, UNCLEAR IMPLICATIONS FOR PATIENTS AND DOCTORS