Makindo Medical Notes

💊 Tamoxifen is a selective oestrogen receptor modulator (SERM) used mainly in the treatment and prevention of oestrogen receptor–positive (ER⁺) breast cancer. It acts as an antagonist in breast tissue but an agonist in bone, uterus, and lipid metabolism. By competitively binding to oestrogen receptors, it inhibits oestrogen-driven tumour growth. The main long-term risk is venous thromboembolism (VTE) and, rarely, endometrial carcinoma.

📘 About

• Always check the BNF entry for current dosing and contraindication guidance.
• Commonly used for adjuvant therapy in ER⁺ breast cancer (pre- or postmenopausal) and for risk reduction in high-risk individuals.
• Also used off-label to induce ovulation in selected infertility cases.

⚙️ Mode of Action

• Competitive antagonist at oestrogen receptors in breast tissue — blocks oestrogen-driven DNA synthesis and cell proliferation.
• Acts as a partial agonist at oestrogen receptors in bone and endometrium — preserving bone density but potentially stimulating uterine lining.
• Overall effect: ↓ recurrence and mortality in ER⁺ breast cancer by reducing tumour cell growth.

💊 Indications & Dose

• Oestrogen receptor–positive breast cancer: Tamoxifen 20 mg PO once daily (usually long-term, up to 5–10 years).
• Fertility induction (off-label): 20 mg PO once daily for 5 days early in menstrual cycle; higher doses may be used under specialist supervision.

💉 Dose Table (Typical Ranges)

🔄 Interactions

• Concurrent use with SSRIs such as paroxetine or fluoxetine may reduce tamoxifen efficacy (inhibits CYP2D6 → ↓ active metabolite endoxifen).
• Increased VTE risk with oestrogen-containing therapies or immobility.
• See BNF for full interaction list.

⚠️ Cautions

• History of VTE or thrombophilia — use with caution; ensure thromboprophylaxis if immobilised.
• Monitor for endometrial changes — report abnormal vaginal bleeding or discharge.
• May cause menstrual irregularity or ovarian cysts in premenopausal women.

🚫 Contraindications

• Pregnancy — teratogenic; ensure contraception during and for at least 2 months after treatment.
• Breastfeeding — avoid use.
• Concurrent coumarin anticoagulant use (relative contraindication due to bleeding risk).

💥 Adverse Effects

• 🔥 Hot flushes and night sweats (due to anti-oestrogenic effects).
• ⬆️ VTE risk (deep vein thrombosis, pulmonary embolism).
• 💧 Vaginal discharge, pruritus, or dryness.
• 🧬 Endometrial hyperplasia or carcinoma (rare; due to uterine agonist activity).
• GI disturbance, nausea, leg cramps, or fluid retention.

🧠 Teaching Note

Tamoxifen exemplifies a drug with tissue-selective receptor modulation — antagonistic in breast, agonistic in bone and endometrium. It improves 10-year survival in ER⁺ breast cancer but requires vigilance for thrombotic and uterine complications. When combined with SSRIs for menopausal symptoms, always select a non-CYP2D6–inhibiting SSRI such as citalopram or sertraline.

📚 References

• BNF: Tamoxifen
• NICE NG101: Early and locally advanced breast cancer (2023)
• EBCTCG (Lancet 2011): 15-year survival benefit from 5 years of adjuvant tamoxifen

🕓 Revisions

• 2025-10 — Expanded and annotated by Dr O’Kane (Makindo edition).