A 24-year-old woman with hormone receptor-positive breast cancer is started on adjuvant tamoxifen. She later presents with abnormal uterine bleeding. Endometrial biopsy shows endometrial hyperplasia. This paradoxical effect of tamoxifen on the uterus is best explained by its classification as a:
- A Selective estrogen receptor degrader (SERD) causing complete estrogen antagonism in all tissues
- B Selective estrogen receptor modulator (SERM) with partial agonist activity in the endometrium ✓
- C Aromatase inhibitor reducing systemic estrogen levels, causing rebound endometrial proliferation
- D Progestin receptor agonist stimulating endometrial growth as an off-target effect
Correct answer: B. Selective estrogen receptor modulator (SERM) with partial agonist activity in the endometrium
Explanation
Tamoxifen is a SERM with mixed agonist/antagonist properties depending on the target tissue. In breast tissue it acts as an estrogen antagonist, but in the endometrium it acts as a partial agonist, which explains the increased risk of endometrial hyperplasia and cancer. SERDs like fulvestrant cause pure antagonism. Aromatase inhibitors (letrozole, anastrozole) do not stimulate the endometrium. The key discriminating fact is the tissue-specific mixed agonist-antagonist profile of SERMs.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.