Tamoxifen

Aka: Tamoxifen

1. See Also
   1. Selective Estrogen Receptor Modulator
2. Indications
   1. Breast Cancer in post-menopausal women
      1. Estrogen Receptor positive
   2. Breast Cancer Prevention in pre-Menopause or post-Menopause with Breast Cancer risk >1.66% in 5 years and age over 35 years old
      1. Higher efficacy than Raloxifene for breast Cancer Prevention, but also higher Venous Thromboembolism and Endometrial Cancer Risks
      2. Unlike Tamoxifen, Raloxifene is not approved for pre-menopausal breast Cancer Prevention
3. Contraindications
   1. Venous Thromboembolism history
   2. Perioperative period
   3. Prolonged immobilization
   4. History of Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA)
4. Efficacy
   1. Estrogen Receptor Positive Breast Cancer
      1. Reduces Breast Cancer recurrence (29%)
      2. Reduces mortality from Breast Cancer (20%)
   2. Reference
      1. (1992) Lancet 339:1-15, 71-85 [PubMed]
5. Course: Following Breast Cancer Management
   1. Original recommendations were for 5 year course following Breast Cancer Management
   2. As of 2013, ten year course is recommended following Breast Cancer Diagnosis
      1. One additional Breast Cancer recurrence prevented for every 27 women who extend their Tamoxifen course from 5 to 10 years
      2. Benefits still outweigh risks of Endometrial Cancer and Venous Thromboembolism
      3. Davies (2012) Lancet 10.1016/S0140-6736(12)61963-1
6. Benefits
   1. Anti-Estrogen
      1. Reduces Breast Cancer recurrence rate
   2. Preserves Bone Mineral Density
      1. Only applies to post-menopausal patients
      2. Bone Mineral Density decreases if premenopausal
   3. Lowers Total Cholesterol and LDL Cholesterol
      1. Only applies to post-menopausal patients
      2. No effect on lipids if premenopausal
7. Dosing
   1. Breast Cancer Prevention: 20 mg daily for 5 years
8. Adverse Effects
   1. Thromboembolism
      1. Tamoxifen significantly increases risk
      2. Associated with 4 cases per 1000 women on Tamoxifen for 5 years
   2. Endometrial Cancer (risks apply to postmenopausal women)
      1. Markedly increased risk if used more than 5 years
      2. Associated with 4 cases per 1000 women on Tamoxifen for 5 years
      3. Relative Risk for 2 to 5 years of use: 2.0
      4. Relative Risk for 5 or more years of use: 6.9
   3. Hot Flashes
      1. See Hot Flashes for management
      2. Avoid symptomatic management with agents contraindicated following Breast Cancer
         1. Avoid Estrogen and Phytoestrogens
         2. Avoid Paroxetine and Fluoxetine (see below)
   4. Cataracts
      1. Eye Exam every 1-2 years
9. Drug Interactions
   1. CYP2D6 Inhibitors (e.g. Paroxetine, Fluoxetine, Bupropion)
      1. May decrease Tamoxifen efficacy (avoid these CYP2D6 Inhibitors in Breast Cancer patients)
10. References
    1. (2002) Lancet 360:817-24 [PubMed]
    2. Bergman (2000) Lancet 356:881-7 [PubMed]