Abstract
BACKGROUND: Although venlafaxine has shown efficacy for hot flashes in hormone receptor–positive breast cancer, evidence in Asian women (especially premenopausal) remains limited. Hot flashes reduce endocrine therapy adherence and severity may increase with ovarian suppression. We conducted a prospective, single-arm, open-label study to evaluate the efficacy and safety of venlafaxine in tamoxifen-treated patients with moderate-to-severe hot flashes. METHODS: Twenty patients received venlafaxine at 37.5 mg/day for 4 weeks, with optional escalation to 75 mg/day. Weekly hot flash scores, adverse events, and serum concentrations of tamoxifen, its metabolites, and venlafaxine (as well as CYP2D6 genotype associations) were assessed. Of the 20 patients, 17 were included in the primary efficacy analysis, 20 in the safety population for adverse events, and 18 in the pharmacokinetic analysis. RESULTS: At Week 4, hot flash scores declined by 49.8% from baseline (P < 0.001). Venlafaxine did not affect serum concentrations of tamoxifen or its metabolites. CYP2D6 intermediate metabolizers had higher venlafaxine concentrations than extensive metabolizers (P = 0.007), although symptom improvement occurred regardless of genotype. All adverse events were Grade 1–2. CONCLUSIONS: These findings demonstrate that venlafaxine safely and effectively alleviates hot flashes in hormone receptor-positive breast cancer patients undergoing tamoxifen-based endocrine therapy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12282-026-01828-5.