Vaginal Estrogen Use in Breast Cancer Survivors: a Systematic Review and Meta-analysis of Recurrence and Mortality Risks

Objective: 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.

Data Sources: 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.

Study Eligibility Criteria: We identified studies that reported on breast cancer recurrence defined per individual review criteria and considered both local and distant recurrence.

Study Appraisal And Synthesis Methods: 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.

Results: 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).

Conclusion: 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.