Use of local estrogen therapy among breast cancer patients in SEER-MHOS database.

Abstract

578 Background: Anti-hormonal therapy with tamoxifen or aromatase inhibitors is a key component in the treatment of hormone receptor-positive breast cancers. One of the adverse effects of this type of therapy is genitourinary syndrome of menopause, which may be treated with vaginal estrogen. It remains unclear whether local vaginal estrogen use carries any increased risk of recurrence or mortality in patients with a history of breast cancer. This has led to conflicting advice in the clinical setting and potentially unnecessary avoidance of hormone-based products that could possibly provide women symptomatic relief. Further exploration of the relationship between local estrogen therapy and breast cancer outcomes is warranted. Methods: A retrospective cohort study of 18,620 female breast cancer patients ≥ 65 years of age diagnosed between 2010-2017 in the SEER-MHOS registry was performed, comparing the breast cancer patients who used local vaginal estrogen (n=800) to those who did not (n=17,820), to assess whether local vaginal estrogen exposure was associated with any difference in overall survival as a primary outcome. Breast cancer specific survival was analyzed as a secondary outcome. Missing data was excluded by complete case analysis. Wilcoxon rank-sum tests were performed to compare continuous variables, Chi-square tests to compare categorical variables, Kaplan-Meier estimation to summarize overall survival, and sub-distribution hazard regression was performed to evaluate breast cancer specific survival by group. Multivariate regression models controlled for age, race, cancer stage, treatment (i.e. surgery, radiation, anti-hormonal therapy), and year of diagnosis. The research protocol was approved by our Scientific Review Committee and submitted for IRB approval. Results: There was a statistically significant increase in overall survival (HR=0.56, p<0.0001) as well as breast cancer-specific survival (HR=0.53, p=0.014) among breast cancer patients who used vaginal estrogen compared to those who did not. Among those who used vaginal estrogen, there was a statistically significant increase in overall survival for those with a duration of use >7 years (median duration of use) compared to those with a duration of use <7 years (HR=0.01, p<0.0001). Subset analysis restricted to patients with hormone positive breast cancer showed a statistically significant increase in overall survival for those who used vaginal estrogen compared to those who did not (HR=0.62, p=0.0007), and a nonsignificant increase in breast cancer specific survival (HR=0.62, p=0.08). Conclusions: The use of vaginal estrogen among this SEER-MHOS cohort of breast cancer patients showed improved survival outcomes. These findings add to a rising contemporary paradigm shift that local hormone therapy is not associated with increased risk to overall or breast cancer specific survival, which has important clinical implications.