1. A RAY OF HOPE: TAMOXIFEN POWERPOINT PRESENTATION BY NEIL RAKHOLIA www.tamoxi.tripod.com

2. OUTLINE: TAMOXIFEN:A RAY OF HOPE 1. TYPES OF BREAST CANCER A. DUCTAL CARCINOMA A. DUCTAL CARCINOMA B. LOBULAR CARCINOMA B. LOBULAR CARCINOMA C. INFLAMMATORY BREAST CANCER C. INFLAMMATORY BREAST CANCER 2. RISK FACTORS A. OLDER AGE A. OLDER AGE B. PERSONAL/ FAMILY HISTORY B. PERSONAL/ FAMILY HISTORY C. HORMONE REPLACEMENT/ ALCOHOL C. HORMONE REPLACEMENT/ ALCOHOL D. EARLY MENARCHE/ NO CHILDREN/ CHILDREN AT LATE AGE D. EARLY MENARCHE/ NO CHILDREN/ CHILDREN AT LATE AGE 3. HORMONE THERAPY WITH TAMOXIFEN A.CHEMICAL STRUCTURE AND SYNTHESIS A.CHEMICAL STRUCTURE AND SYNTHESIS B.GENERAL B.GENERAL i. MECHANISM OF ACTION i. MECHANISM OF ACTION ii. SIDE EFFECTS ii. SIDE EFFECTS C. INDICATION AND USAGE C. INDICATION AND USAGE i. METASTATIC BREAST CANCER i. METASTATIC BREAST CANCER ii. DUCTAL CARCINOMA IN SITU ii. DUCTAL CARCINOMA IN SITU iii. PREVENTION IN HIGH RISK WOMEN iii. PREVENTION IN HIGH RISK WOMEN D. FUTURE DIRECTION D. FUTURE DIRECTION i. TAMOXIFEN AS PREVENTIVE MEASURE i. TAMOXIFEN AS PREVENTIVE MEASURE ii. BIPHOSPHONATES ii. BIPHOSPHONATES iii. HERCEPTIN/ MONOCLONAL ANTIBODY iii. HERCEPTIN/ MONOCLONAL ANTIBODY

3. BREAST CANCER EPIDEMIOLOGY * FDA The National Cancer Institute estimates that 13.4 percent of women born today will be diagnosed with breast cancer at some time in their lives The National Cancer Institute estimates that 13.4 percent of women born today will be diagnosed with breast cancer at some time in their lives In 1070’s risk of getting breast cancer was “1 in 10”, now it is “1 in 7” In 1070’s risk of getting breast cancer was “1 in 10”, now it is “1 in 7” This increase in risk may be due to better diagnostic tests, increase in age, changes in life style This increase in risk may be due to better diagnostic tests, increase in age, changes in life style

4. TYPES AND RISK FACTORS OF BREAST CANCER * NEJM DUCTAL CARCINOMA DUCTAL CARCINOMA LOBULAR CARCINOMA LOBULAR CARCINOMA INFLAMMATORY BREAST CANCER INFLAMMATORY BREAST CANCER OLDER AGE OLDER AGE STARING PERIOD AT EARLY AGE STARING PERIOD AT EARLY AGE OLDER AGE AT FIRST CHILD OR NO CHILD OLDER AGE AT FIRST CHILD OR NO CHILD FAMILY HISTORY FAMILY HISTORY ALCOHOL/ HORMONE USE ALCOHOL/ HORMONE USE BEING WHITE BEING WHITE

5. TREATMENT 0F BREAST CANCER * BARR THERE ARE FOUR MAJOR TYPES TREATMENT IS USED  SURGERY RADIATION RADIATION HORMONE THERAPY HORMONE THERAPY CHEMOTHERAPY CHEMOTHERAPY TAMOXIFEN IS CONSIDERED AS NON-STEROIDAL ANTI ESTROGEN IT BLOCKS THE ESTROGEN FROM BINDING TO THE CANCERCELLS AND THUS INHIBITING THEIR GROWTH

6. SYNTHESIS I. SHIINA AND M. SUZUKI APPROCHED THE SYNTHESIS OF TAMOXIFEN BY TETRASUBSTITUTED ALKENE CORE OF TAMOXIFEN BY SUCCESIVE ALLYYLATION OF AROMATIC ALDEHYDES AND A FRIEDEL-CRAFTS ALKYLATION, FOLLOWED BY MIGRATION OF DOUBLE BOND. THE STARTEGY WAS TYPICALLY CARRIED OUT AS A 3 COMPONENT COUPLING REACTION AMONG BENZALDEHYDE,CINNAMYLTRIMETHYLSILANE AND ANISOLE WITH HfCL4 AND TRIMETHYLSILYLTRIFLUOROMETHANESULFONATE I. SHIINA AND M. SUZUKI APPROCHED THE SYNTHESIS OF TAMOXIFEN BY TETRASUBSTITUTED ALKENE CORE OF TAMOXIFEN BY SUCCESIVE ALLYYLATION OF AROMATIC ALDEHYDES AND A FRIEDEL-CRAFTS ALKYLATION, FOLLOWED BY MIGRATION OF DOUBLE BOND. THE STARTEGY WAS TYPICALLY CARRIED OUT AS A 3 COMPONENT COUPLING REACTION AMONG BENZALDEHYDE,CINNAMYLTRIMETHYLSILANE AND ANISOLE WITH HfCL4 AND TRIMETHYLSILYLTRIFLUOROMETHANESULFONATE

7. INDICATION/USES AND SIDE EFFECTS of TAMOXIFEN METASTATIC BREAST CANCER METASTATIC BREAST CANCER ADJUVENT TREATMENT OF BREAST CANCER ADJUVENT TREATMENT OF BREAST CANCER DUCTAL CARCINOMA IN SITU DUCTAL CARCINOMA IN SITU MCCUNE-ALBRIGHT SYNDROME MCCUNE-ALBRIGHT SYNDROME REDUCTION IN INCIDENCE OF HIGH RISK PATIENTS REDUCTION IN INCIDENCE OF HIGH RISK PATIENTS DISCHARGE HOT FLASHES, VAGINAL, MENSTRUAL IRREGULARITIES, HAIR LOSS, SKIN CHANGES, SKIN RASHES, HEADACHE, DISCHARGE HOT FLASHES, VAGINAL, MENSTRUAL IRREGULARITIES, HAIR LOSS, SKIN CHANGES, SKIN RASHES, HEADACHE, BLOOD CLOTS IN THE VEINS BLOOD CLOTS IN THE VEINS ENDOMETRIAL CANCER ENDOMETRIAL CANCER STROKE STROKE

8. NSABP B-24 TRIAL PRIMARY OBJECTIVE IS TO DETERMINE IF TAMOXIFEN REDUCE INCIDENCE OF RECURRANCE TYPE OF EVENT LUMPACTOMY,RADIOTHERA PY AND PLACEBO #EVENTS PER 1000 LUMPACTOMY, RADIOTHERAPY AND TAMOXIFEN RELATIVE RISK INVASIVE BREAST CANCER 74 16.73 44 9.60 0.57 IPSILATERAL 47 10.61 27 5.90 0.56 CONTRALATERAL 25 5.64 17 3.71 0.66 SECONDARY END POINTS DCIS 56 12.66 41 8.95 0.71 IPSILATERAL 46 10.40 38 8.29 0.88 CONTRALATERAL 10 2.26 03 0.65 0.29 UTERINE MALIGNANCIES 04092.25

9. MECHANISM OF ACTION AND SYNTHESIS TAMOXIFEN ACTS AS AN ANTI ESTROGEN TAMOXIFEN ACTS AS AN ANTI ESTROGEN IT BINDS TO THE BREAST CANCER CELLS COMPETITIVELY TO THE ESTROGEN IT BINDS TO THE BREAST CANCER CELLS COMPETITIVELY TO THE ESTROGEN ESTROGEN STIMULATES THE GROWTH OF THE TUMOR AND TAMOXIFEN INHIBITS THE GROWTH OF THE TUMOR ESTROGEN STIMULATES THE GROWTH OF THE TUMOR AND TAMOXIFEN INHIBITS THE GROWTH OF THE TUMOR

10. FUTURE DIRECTION BREAST CANCER IS A SECOND LEADING CAUSE OF DEATH IN AMERICAN WOMEN AND ACCOUNTS FOR 31 PERCENT OF ALL CANCER IN WOMEN BREAST CANCER IS A SECOND LEADING CAUSE OF DEATH IN AMERICAN WOMEN AND ACCOUNTS FOR 31 PERCENT OF ALL CANCER IN WOMEN IN 1998, FDA APPROVED TAMOXIFEN AS PREVENTIVE DRUG FOR HIGH RISK WOMEN IN 1998, FDA APPROVED TAMOXIFEN AS PREVENTIVE DRUG FOR HIGH RISK WOMEN TAMOXIFEN IS IN THE MARKET FOR OVER 20 YEARS TAMOXIFEN IS IN THE MARKET FOR OVER 20 YEARS

11. FUTURE DIRECTION HECEPTIN (TRASTUZUMAB) HECEPTIN (TRASTUZUMAB) MONOCLONAL GROWTH FACTOR ANTIBODY MONOCLONAL GROWTH FACTOR ANTIBODY ZOLONDRONATE DOES KILL THE CANCER CELLS? ZOLONDRONATE DOES KILL THE CANCER CELLS?

12. BIBLIOGRAPHY http://www.nsabp.pitt.edu/B-24.htm http://www.nsabp.pitt.edu/B-24.htm http://www.fda.gov/cder/news/tamoxifen/default.htm http://www.fda.gov/cder/news/tamoxifen/default.htm http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html ?DOC=heartcut%5carchive%5c020904_heartcut.html#3 http://www.chemistry.org/portal/a/c/s/1/acsdisplay.html ?DOC=heartcut%5carchive%5c020904_heartcut.html#3 http://www.moffitt.usf.edu/pubs/ccj/v6n3/dept1.htm http://www.moffitt.usf.edu/pubs/ccj/v6n3/dept1.htm http://www.nejm.org http://www.nejm.org http://www.barrlabs.com/packageinsert http://www.barrlabs.com/packageinsert