Survival Outcomes in Breast Cancer Patients With Use of Vaginal Estrogen Therapy: A SEER Analysis

PURPOSE Antihormonal therapy, including tamoxifen or aromatase inhibitors, is central to the treatment of hormone receptor–positive breast cancers. A common adverse effect is genitourinary syndrome of menopause, which may be treated with vaginal estrogen. However, the safety of vaginal estrogen in breast cancer survivors remains controversial, leading to inconsistent clinical guidance and potential underuse. METHODS We conducted a retrospective cohort study of 25,874 female patients with breast cancer age 65 years and older diagnosed between 2007 and 2017 using the SEER-Medicare Health Outcomes Survey (MHOS) registry. Patients who used vaginal estrogen after diagnosis (n = 1,053) were compared with nonusers (n = 24,821). Multivariable Cox proportional hazard models evaluated associations with overall and cause-specific mortality, adjusting for demographics, comorbidities, and oncologic factors. A secondary analysis modeled vaginal estrogen use as a time-dependent covariate. RESULTS Vaginal estrogen use was associated with decreased overall mortality (adjusted hazard ratio [HR], 0.49; P < .01) and cause-specific mortality (adjusted HR, 0.31; P = .01). However, these associations were attenuated and no longer significant in time-dependent analysis. Among patients with hormone receptor–positive breast cancer, vaginal estrogen use was associated with reduced overall mortality (adjusted HR, 0.58; P = .02), although this lost significance in the time-dependent model. A nonsignificant reduction in cause-specific mortality was observed within this subgroup (adjusted HR, 0.45, P = .11). CONCLUSION Vaginal estrogen use was not associated with worse overall survival or breast cancer–specific survival in this cohort SEER-MHOS cohort of patients older than 65 years. Loss of significance in time-dependent models suggests that initial associations may reflect immortal time or selection bias. These findings support growing evidence that local vaginal estrogen is not associated with adverse survival outcomes and may be considered for symptom management in appropriately selected patients.