2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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)

9. 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

10. 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

11. 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

12. . 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

13. 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