Detailed definition
Tamoxifen is a SERM that has been the foundation of adjuvant endocrine therapy for hormone-receptor-positive breast cancer since the 1970s. It binds estrogen receptors and acts as an antagonist in breast tissue but as a partial agonist in endometrium and bone. Standard adjuvant duration is 5–10 years. Side effects include hot flashes (60–80% of women), GSM, mood symptoms, an approximately 2× increase in endometrial cancer risk (still rare in absolute terms), and a small increase in VTE risk (similar to oral estrogen). Tamoxifen is metabolized to its active form (endoxifen) by CYP2D6, so strong CYP2D6 inhibitors — including paroxetine and fluoxetine — should be avoided in tamoxifen patients, while venlafaxine and gabapentin are preferred for hot flash management.
Why it matters in menopause
For premenopausal breast cancer survivors on tamoxifen who develop severe hot flashes, the choice of non-hormonal therapy matters: avoid paroxetine and fluoxetine (CYP2D6 inhibitors), favor venlafaxine, gabapentin, or fezolinetant. Vaginal estrogen for GSM is generally permitted at low doses with oncology team OK.
Related terms
Sources
External references: Wikipedia.