A RAY OF HOPE: TAMOXIFEN

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A RAY OF HOPE TAMOXIFEN

• POWERPOINT PRESENTATION BY
• NEIL RAKHOLIA
• www.tamoxi.tripod.com

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OUTLINETAMOXIFENA RAY OF HOPE

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

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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
• In 1070s 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

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TYPES AND RISK FACTORS OF BREAST CANCER NEJM

• DUCTAL CARCINOMA
• LOBULAR CARCINOMA
• INFLAMMATORY BREAST CANCER

• OLDER AGE
• STARING PERIOD AT EARLY AGE
• OLDER AGE AT FIRST CHILD OR NO CHILD
• FAMILY HISTORY
• ALCOHOL/ HORMONE USE
• BEING WHITE

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TREATMENT 0F BREAST CANCER BARR

• THERE ARE FOUR MAJOR TYPES TREATMENT IS USED
• SURGERY
• RADIATION
• HORMONE THERAPY
• CHEMOTHERAPY
• TAMOXIFEN IS CONSIDERED AS NON-STEROIDAL ANTI
  ESTROGEN
• IT BLOCKS THE ESTROGEN FROM BINDING TO THE
  CANCERCELLS AND THUS INHIBITING THEIR GROWTH

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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 TRIMETHYLSILYLTRIFLUOROMETHANESULFO
  NATE

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INDICATION/USES AND SIDE EFFECTS of TAMOXIFEN

• METASTATIC BREAST CANCER
• ADJUVENT TREATMENT OF BREAST CANCER
• DUCTAL CARCINOMA IN SITU
• MCCUNE-ALBRIGHT SYNDROME
• REDUCTION IN INCIDENCE OF HIGH RISK PATIENTS

• DISCHARGE HOT FLASHES, VAGINAL, MENSTRUAL
  IRREGULARITIES, HAIR LOSS, SKIN CHANGES, SKIN
  RASHES, HEADACHE,
• BLOOD CLOTS IN THE VEINS
• ENDOMETRIAL CANCER
• STROKE

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NSABP B-24 TRIAL PRIMARY OBJECTIVE IS TO
DETERMINE IF TAMOXIFEN REDUCE INCIDENCE OF
RECURRANCE
TYPE OF EVENT LUMPACTOMY,RADIOTHERAPY 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 04 09 2.25
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MECHANISM OF ACTION AND SYNTHESIS

• TAMOXIFEN ACTS AS AN ANTI 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

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FUTURE DIRECTION

• 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
• TAMOXIFEN IS IN THE MARKET FOR OVER 20 YEARS

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FUTURE DIRECTION

• HECEPTIN (TRASTUZUMAB)
• MONOCLONAL GROWTH FACTOR ANTIBODY
• ZOLONDRONATE DOES KILL THE CANCER CELLS?

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BIBLIOGRAPHY

• http//www.nsabp.pitt.edu/B-24.htm
• http//www.fda.gov/cder/news/tamoxifen/default.htm
  
• http//www.chemistry.org/portal/a/c/s/1/acsdisplay
  .html?DOCheartcut5carchive5c020904_heartcut.htm
  l3
• http//www.chemistry.org/portal/a/c/s/1/acsdisplay
  .html?DOCheartcut5carchive5c020904_heartcut.htm
  l3
• http//www.moffitt.usf.edu/pubs/ccj/v6n3/dept1.htm
  
• http//www.nejm.org
• http//www.barrlabs.com/packageinsert