A 45-year-old woman on tamoxifen for 3 years (5-year planned course) is found to be a CYP2D6 poor metabolizer. What is the most clinically significant implication of this pharmacogenomic finding?
- A Higher risk of tamoxifen-induced thromboembolism
- B Reduced conversion to endoxifen, decreasing efficacy ✓
- C Increased risk of tamoxifen-related uterine carcinoma
- D Tamoxifen accumulation causing exaggerated hot flushes
Correct answer: B. Reduced conversion to endoxifen, decreasing efficacy
Explanation
Tamoxifen requires hepatic conversion to its active metabolite endoxifen via CYP2D6. CYP2D6 poor metabolizers generate substantially lower endoxifen plasma levels, correlating with reduced breast cancer recurrence protection. This is clinically relevant because concurrent use of strong CYP2D6 inhibitors (e.g., paroxetine, fluoxetine) mimics poor metabolizer status and should be avoided in women on tamoxifen. Thromboembolic risk is related to the estrogen-agonist effect on coagulation factors, not CYP2D6 status. Uterine effects are class effects of tamoxifen itself.
Reference: Bailey & Love's Short Practice of Surgery, 27th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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