Use and effectiveness of adjuvant ovarian function suppression (OFS) in premenopausal women with early breast cancer

Abstract

Background: OFS either in association with tamoxifen (TAM) or an aromatase inhibitor (AI) improved disease-free survival in young women (≥35) and in those premenopausal women at higher risk of recurrence. However, its survival benefit remains largely unknown. In this study we characterize real-world use of adjuvant OFS from 2006 to 2015 and analyze its overall survival (OS) impact. Methods: Retrospective observational cohort study of premenopausal women with Stage I-III hormone receptor-positive (HR+) breast cancer treated at one of 5 large centers in Portugal and diagnosed from 2006-2015. Study outcomes were use of OFS and OS. Pearson's Chi2 test, logistic regression and Cox proportional hazards models were used. Results: Of 1717 eligible patients, 304 (17.3%) were treated with adjuvant OFS, of which 271 (15.4%) in combination with TAM and 33 (1.9%) with AI. Baseline characteristics differed by subgroups: patients treated with OFS were younger, had larger, less differentiated (grade III 16% vs 24% for OFS), more frequently HER2 positive (14% vs. 19% for OFS) tumors, and underwent more frequently mastectomy (48% vs 57% for OFS), radiotherapy (25% vs 31% for OFS) and (neo)adjuvant chemotherapy (73% vs 79% for OFS). Adjuvant OFS was used at least since 2006 with an increase in its use from 2014 onward (16% vs 25% since 2014), particularly for the combination with AI (0.4% vs 8% since 2014). In a multivariate model, characteristics associated with use of OFS included younger age and year of diagnosis≥2014 (both p<0.001). Median time on OFS was 25 mo. (interquartile range 21-27). With a median follow-up of 38 mo. (IQR 20-66) and after controlling for age at diagnosis, staging, histologic grade, HER2 status, use of (neo)adjuvant CT, type of surgery and year of diagnosis, patients treated with OFS had a better OS when compared to those not treated with OFS (adjusted-HR 0.44, 95% CI 0.19-0.96; p=0.040). Absolute benefit at year 5 was 2.1% (93.2 [95% CI 90.8 - 94.9) vs 95.3 [95% CI 89.7 - 97.9]). Conclusions: In the real-world setting, a quarter of premenopausal women with early breast cancer were already treated with adjuvant OFS in 2014. After a median follow-up of 3 years, adjuvant OFS showed an OS benefit.