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Tamoxifen

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Tamoxifen

  • See Also
  1. Selective Estrogen Receptor Modulator
  • Indications
  1. Breast Cancer in post-menopausal women (Estrogen Receptor positive)
    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. Breast Cancer recurrence prevention (NNT 27) who extend their Tamoxifen course from 5 to 10 years
      2. Benefits still outweigh risks of Endometrial Cancer and Venous Thromboembolism
      3. Davies (2013) Lancet 381(9869):805-16 +PMID: 23219286 [PubMed]
  2. Breast Cancer Prevention in pre-Menopause or post-Menopause
    1. Breast Cancer risk >1.66% in 5 years and age over 35 years old
    2. Higher efficacy than Raloxifene for breast Cancer Prevention
    3. However also higher Venous Thromboembolism and Endometrial Cancer Risks
    4. Unlike Tamoxifen, Raloxifene is not approved for pre-menopausal breast Cancer Prevention
  • Contraindications
  1. Venous Thromboembolism history
  2. Perioperative period
  3. Prolonged immobilization (discontinue 72 hours before expected immobilization)
  4. History of Cerebrovascular Accident (CVA) or Transient Ischemic Attack (TIA)
  • Mechanism
  1. See Selective Estrogen Receptor Modulator
  2. Positive Estrogen effects
    1. Stimulates bone mineralization
    2. Improves lipid profile
  3. Anti-Estrogenic effects
    1. No Breast stimulation
    2. No uterine stimulation
  • Dosing
  1. Breast Cancer
    1. Tamoxifen 10 to 20 mg orally twice daily for 5 to 10 years
  2. Breast Cancer Prevention
    1. Tamoxifen 20 mg daily for 5 years
  • Adverse Effects
  1. Precautions
    1. Thromboembolism, Uterine Cancer and Cardiovascular Risk are FDA black box warnings
  2. Thromboembolism
    1. Tamoxifen significantly increases risk
    2. Associated with 4 cases per 1000 women on Tamoxifen for 5 years
  3. 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
  4. 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)
  5. Other adverse effects
    1. Alopecia
    2. Cataracts
      1. Eye Exam every 1-2 years
    3. Lab abnormalities
      1. Hypercalcemia
      2. Liver Function Test abnormalities
  • Safety
  1. Avoid in Lactation
  2. Avoid in pregnancy
    1. Use reliable Contraception for at least 2 months after completing Tamoxifen
  3. Monitoring
    1. Complete Blood Count
    2. Liver Function Tests
  • Efficacy
  1. Estrogen Receptor Positive Breast Cancer
    1. Reduces Breast Cancer recurrence (29%)
    2. Reduces mortality from Breast Cancer (20%)
  2. Anti-Estrogen
    1. Reduces Breast Cancer recurrence rate
  3. Preserves Bone Mineral Density
    1. Only applies to post-menopausal patients
    2. Bone Mineral Density decreases if premenopausal
  4. Lowers Total Cholesterol and LDL Cholesterol
    1. Only applies to post-menopausal patients
    2. No effect on lipids if premenopausal
  5. Reference
    1. (1992) Lancet 339:1-15, 71-85 [PubMed]
  • Drug Interactions
  1. CYP2D6 Inhibitors (e.g. Paroxetine, Fluoxetine, Bupropion)
    1. May decrease Tamoxifen efficacy (avoid these CYP2D6 Inhibitors in Breast Cancer patients)
  2. Oral Anticoagulants
    1. Tamoxifen may effect bleeding risk
  • Resources
  1. Tamoxifen (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7ee3d3d2-85d1-4018-8e70-5ed8a64ae1f0
  • References
  1. (2002) Lancet 360:817-24 [PubMed]
  2. Bergman (2000) Lancet 356:881-7 [PubMed]