Tamoxifen

• Hormone Receptor-Positive Breast Cancer
• Breast Cancer Prevention
• DCIS
• Metastatic Breast Cancer

Tamoxifen is a selective estrogen receptor modulator (SERM) that has been a cornerstone of hormone receptor-positive breast cancer treatment for decades. It acts as an estrogen antagonist in breast tissue while having estrogen agonist effects in other tissues.

Mechanism of Action

Tamoxifen exhibits tissue-selective effects:

• Estrogen receptor binding: Binds to estrogen receptors (ER-alpha and ER-beta)
• Breast tissue antagonism: Blocks estrogen-stimulated breast cancer cell proliferation
• Bone agonism: Maintains bone density in postmenopausal women
• Uterine agonism: Stimulates endometrial growth (concerning for endometrial cancer risk)
• Lipid agonism: Favorable effects on lipid profile

Tamoxifen is a prodrug; its metabolites (endoxifen, 4-hydroxytamoxifen) are more potent.

Available Formulations

Tamoxifen is available as:

• Tablets: 10 mg, 20 mg
• Oral solution: 10 mg/5 mL

Medical Uses

FDA-Approved Indications:

• Adjuvant treatment of breast cancer after primary treatment (surgery, radiation)
• Metastatic breast cancer in women and men
• Reduction of breast cancer incidence in high-risk women
• Reduction of contralateral breast cancer in patients with DCIS after surgery and radiation

Typically used for 5-10 years in the adjuvant setting.

Dosing Guidelines

Breast Cancer Treatment (Adjuvant or Metastatic):

• 20-40 mg daily (usually 20 mg once daily)
• Duration: 5-10 years for adjuvant treatment

Breast Cancer Risk Reduction:

• 20 mg daily for 5 years

Ductal Carcinoma In Situ (DCIS):

• 20 mg daily for 5 years

Administration:

• May be taken with or without food
• Usually given as a single daily dose

Important Safety Information

Boxed Warning:

• Serious and life-threatening events including uterine malignancies, stroke, and pulmonary embolism

Contraindications:

• History of deep vein thrombosis or pulmonary embolism (for risk reduction use)
• Concomitant warfarin therapy (for risk reduction use)
• Pregnancy
• Known hypersensitivity

Warnings and Precautions:

• Endometrial cancer: 2-7x increased risk; report abnormal vaginal bleeding
• Thromboembolic events: DVT, PE, stroke risk increased
• Ocular effects: Cataracts, retinopathy, optic neuropathy
• Hepatotoxicity: Rare but serious
• Hypercalcemia: May occur with bone metastases
• CYP2D6 inhibitors: May reduce efficacy

Drug Interactions

Strong CYP2D6 Inhibitors (paroxetine, fluoxetine, bupropion, quinidine):

• Reduce conversion to active metabolite endoxifen; avoid if possible

Moderate CYP2D6 Inhibitors (duloxetine, sertraline):

• May modestly reduce efficacy; consider alternatives

Warfarin:

• Significant interaction; increased INR; avoid combination for risk reduction

CYP3A4 Inducers (rifampin):

• May reduce tamoxifen levels

Letrozole:

• Tamoxifen reduces letrozole levels; avoid concurrent use

Special Populations

• CYP2D6 Poor Metabolizers: Reduced endoxifen levels; may have lower efficacy
• Hepatic Impairment: No specific guidelines; use with caution
• Renal Impairment: No adjustment needed
• Pregnancy: Contraindicated (Category D); use effective contraception
• Premenopausal Women: Effective contraception required
• Men: Approved for breast cancer treatment