Class & Mechanism

Selective Estrogen Receptor Modulator (SERM) – antagonist on breast estrogen receptors, partial agonist in bone and endometrium.
Blocks estrogen-driven tumor growth in ER+ breast tissue while preserving bone density in postmenopausal women.

Indications (Oncology Focus)

Adjuvant treatment of ER+ breast cancer (premenopausal & postmenopausal).
Metastatic ER+ breast cancer.
Breast cancer risk reduction in high-risk patients (e.g., LCIS, BRCA carriers, Gail model ≥ 1.66%).

Dose: Typically 20 mg PO once daily (duration 5–10 years depending on stage/risk).
Key adverse effects: hot flashes, vaginal discharge, menstrual irregularities.
Serious risks: ↑ venous thromboembolism (DVT/PE), ↑ endometrial cancer risk (due to uterine ER agonism), cataracts.
Drug interactions: CYP2D6 metabolism → avoid strong inhibitors (e.g., paroxetine, fluoxetine) which can reduce active metabolite endoxifen levels.
Monitoring: signs of VTE, abnormal vaginal bleeding (endometrial evaluation), adherence.
Counseling: Emphasize benefit-risk discussion in prevention setting; advise reporting leg swelling, shortness of breath, or unusual bleeding.

Often used as chemoprevention to reduce progression to invasive ductal/lobular carcinoma — 5-year therapy can reduce risk by ~50% in high-risk women.