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CELLULAR BIOLOGY IN BREAST CANCER

CELLULAR BIOLOGY IN BREAST CANCER . JESSE ELLMAN MD SEPT 2010 CLINICAL ASSISTANT PROFESSOR DEPT OB GYN AND WOMENS HEALTH WE MAY BE ENTERING A NEW PHASE IN MEDICINE IN DIAGNOSIS AND TREATMENT OF MANY TUMORS. CELLULAR BIOLOGY IN BREAST CANCER. PLAYS A PART IN TWO MAJOR AREAS

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CELLULAR BIOLOGY IN BREAST CANCER

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  1. CELLULAR BIOLOGY IN BREAST CANCER JESSE ELLMAN MD SEPT 2010 CLINICAL ASSISTANT PROFESSOR DEPT OB GYN AND WOMENS HEALTH WE MAY BE ENTERING A NEW PHASE IN MEDICINE IN DIAGNOSIS AND TREATMENT OF MANY TUMORS

  2. CELLULAR BIOLOGY IN BREAST CANCER • PLAYS A PART IN TWO MAJOR AREAS • 1.TARGETED THERAPY • 2.PROGNOSTICATION OF RECURRENCES • IS THE STUDY OF GENES,ENZYMES AND CELLULAR FUNCTION-MICROBIOLOGY-AS APPLIED TO TREATMENT OF BREAST CANCER

  3. UP TO DATE CONCEPTS OF TREATMENT • TO TAKE THE LABORATORY FINDINGS TO THE BEDSIDE AS NEW DRUG THERAPIES—MAJOR PROJECTS • CHEMOTHERAPY KILLS CELLS • IDEAL IS TO TREAT CANCER WITHOUT KILLING NORMAL CELLS

  4. TARGETED THERAPY • A MONOCLONAL ANTIBODY THAT AIMS AT EPITHELIAL GROWTH FACTOR—THE DRUG HERCEPTIN..A TYROSINE KINASE INHIBITOR..STRONGER ONES TO COME (TYKERB,HERCEPTIN DM1).WILL WORK IN HERCEPTIN FAILURES • HSP-90 INHIBITORS .INHIBITS HSP-90 CHAPERONE FUNCTION ON ESTROGEN

  5. TARGETED THERAPY • ANOTHER MONOCLONALANTIBODY THAT AIMS AT VASCULAR ENDOTHELIUM GROWTH FACTOR IS CALLED AVASTIN-USED IN COLON CANCER . IN BREAST IT INCREASED TUMOR FREE INTERVAL BUT NOT LIFE EXPECTANCY..MAY LOSE APPROVAL BY FDA • SERMS(SERUM ESTROGEN RECEPTOR MODULATERS) (TAMOXIFEN AND EVISTA) COMPETES WITH ESTROGEN FOR ESTROGEN RECEPTOR FUNCTION

  6. TARGETED THERAPY • AROMATASE INHIBITORS-ATTACK ENZYME THAT MAKES ESTROGEN FROM TESTOSTERONE • HEAT SHOCK PROTEINS ACT AS CHAPERONES FOR ESTROGEN RECEPTOR BREAST CA-NEW DRUGS INHIBIT HEAT SHOCK PROTEINS

  7. CELLULAR BIOLOGY AS PROGNOSTICATOR • PRESENTLY GENOMICS (ONCOTYPE DX) IS A 21 GENE TEST USED IN ER+/PR+ PTS FOR PROGNOSIS • IN EUROPE 71 GENE TEST IS BEING USED TO DEVELOP RECURRENCE RISK(MAMAPRINT)

  8. CELLULAR BIOLOGY AS PROGNOSTICATOR • KI-67 PROLIFERATION INDEX MEASURES CELLULAR POTENTIAL FOR DIVISION.HIGHER SCORE SHOWS GREATER RECURRENCE • DR, MARC LIPPMAN,MIAMI UNIVERSITY—GENOMIC FINDING OF GREB 1,A GENE- WHICH MEDIATES ESTROGENIC STIMULATION ABILITY –ATTEMPT TO SILENCE THIS GENE AS THERAPY OR ESTABLISH RESPONSE TO HORMONE THERAPY KNOWING VOLUME OF GREB 1 TYPE GENES

  9. DCIS PROGNOSTICATOR • IF P16,COX-2 AND K167 ALL ELEVATED THERE IS A 5 TIMES GREATER RISK OF RECURRENT INVASIVE CANCER • TRIPLE POSITIVE DCIS IS VERY DIFFERENT FROM TRIPLE NEGATIVE INVASIVE CANCER

  10. CELLULAR BIOLOGY • ALLOWS PTS TREATMENT TO BE INDIVIDUALIZED I.E FOR MORE OR LESS AGGRESSIVE TREATMENT (SOME CASES MAY NOT NEED CHEMO) • NOW RECOGNIZE 5 SUBTYPES OF BREAST CANCER WITH DIFFERENT MOLECULAR CHEMISTRIES

  11. . BR CA 1/BR CA 2 • MUTATED GENES OF BRCA1/BRCA2 CANNOT REPAIR DNA DAMAGE CELLS • NORMAL CELL DNA REPAIR DONE BY POLY ADP-RIBOSE POLYMERASE- (PARP’S) • IF INHIBIT PARP’S WITH NEW DRUG.(OLAPARIB)--THE PT WITH BRCA/1BR/CA 2 WHO ALREADY HAVE THE DEFECTIVE REPAIR…THE CANCER CELLS WILL DIE

  12. ENDOMETRIAL CANCER GROWTH FACTORS • M TOR INHIBITORS- BLOCK GROWTH PATHWAYS IN ENDOMETRIAL CANCERS • TRIAL OF ANTI-ANGIOGENIC DRUG (AVASTIN ) TO BE DONE IN ENDOMETRIAL CANCER • A NEW AGE OF MEDICINE IS COMING

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