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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

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BREAST CANCER INCIDENCE

BY RACE 2006-2010

BREAST CANCER – THE PAST

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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

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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

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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

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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

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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

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HER 2 + BREAST CANCER ADO TRASTUZUMAB EMTANSINE(TDM-1) – “MAGIC BULLET”

ADO TRASTUZUMAB

EMTANSINE (TDM-1)T-DM1 / ASCO 2012

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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

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SYNTHETIC LETHALITY:

BRCA+ & SPORADIC “BRCANESS”

METASTATIC TRIPLE

NEGATIVE BREAST CANER

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BREAST CANCER THERAPY BREAST CANCER ADJUVANT

ADJUVANT CHEMOTHERAPY ADJUVANT CHEMOTHERAPY

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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

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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