Vaginal estrogen use in breast cancer survivors: a systematic review and meta-analysis of recurrence and mortality risks

To assess the risk of breast cancer recurrence, breast cancer-specific mortality, and overall mortality for breast cancer survivors receiving vaginal estrogen therapy for genitourinary syndrome of menopause. From the inception of each database to April 6th, 2024, a systematic literature search was conducted in Google Scholar, PubMed, EMBASE, CINAHL, NCBI, and Science Direct. A secondary search was conducted on September 26th, 2024 utilizing Google Scholar, PubMed, EMBASE, CINAHL, and Science Direct. We identified studies that reported on breast cancer recurrence defined per individual review criteria and considered both local and distant recurrence. Three reviewers evaluated studies with eligibility criteria in mind. Breast cancer recurrence was the primary outcome. The secondary outcomes included: breast cancer mortality and overall mortality. Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model. We assessed the 95% prediction intervals to calculate the likely range within which we can expect to observe future individual values, based on a current model or dataset. We calculated the fragility index to evaluate the robustness of the pooled estimates. Of 5522 articles identified, 8 observational studies were included in this meta-analysis. The use of vaginal estrogen in patients with a history of breast cancer was not associated with an increased risk of breast cancer recurrence (6 articles, 24,060 patients, odds ratio, 0.48; 95% confidence interval, 0.23–0.98). There was no increase in the risk of breast cancer mortality (4 articles, 61,695 patients, odds ratio 0.60; 95% confidence interval 0.18–1.95). Lastly, there was no increase in overall mortality with use of vaginal estrogen in breast cancer survivors (5 articles 59,724, odds ratio 0.46; 95% confidence interval 0.42–0.49). The use of vaginal estrogen in patients with a history of breast cancer does not appear to be associated with an increased risk of breast cancer recurrence, breast cancer-specific mortality, or overall mortality.