Updated survival outcomes and predictors of benefit from ovarian function suppression in premenopausal women with hormone-receptor-positive breast cancer: Results from the ASTRRA trial.

Abstract

Background: The ASTRRA trial previously demonstrated that adding ovarian function suppression (OFS) to tamoxifen (TAM) showed consistent disease free survival (DFS) benefit at 8-yr follow-up analysis in premenopausal women with hormone-receptor (HR)–positive breast cancer who remain premenopausal or resume menstruation after chemotherapy. Here, we aimed to update the survival outcomes and identify patients most likely to benefit from OFS to tailor clinical decision-making. Methods: A total of 1,282 premenopausal women were randomized 1:1 to receive either 5 years of TAM alone (TAM-only) or 5 years of TAM with OFS for 2 years (TAM + OFS). The primary endpoint was DFS, and the secondary endpoint was overall survival (OS). For the HER2-negative cohort, a composite risk score (range: 0–5) for breast cancer-free interval (BCFI) was calculated based on tumor size, nodal status, and tumor grade using a Cox regression model. The impact of OFS was analyzed by composite risk score and stratified by age. The events for BCFI were defined as local, regional, or distant recurrence; invasive contralateral breast cancer; or death resulting from breast cancer as the first event. Results: With a median follow-up of 117.6 months, the 10-year DFS rate was 83.7% in the TAM + OFS group compared to 75.9% in the TAM-only group (hazard ratio [HR], 0.68; 95% CI, 0.53-0.87). Meanwhile, there were no significant differences in 10-year OS: 94.6% in the TAM + OFS vs. 93.2% in the TAM-only group (HR, 0.79; 95% CI, 0.50-1.27). In the 776 patients with HER2-negative breast cancer, there were no significant differences in the distribution of age group (P = .320), tumor size (P = .572), lymph node status (P = .577), or histologic grade (P = .249) between TAM + OFS and TAM-only groups. Worse 10-year BCFI was significantly associated with younger age ( < 40 vs. 40-45 years, P = .026), larger tumor size (≥ 2cm vs. < 2cm, P < .001), lymph node positivity (positive vs. negative, P < .001), and aggressive histologic grade (III vs. II vs. I, P = .006), respectively. Among patients with a high composite risk score (4–5, n = 282, 36.3% of the HER2-negative cohort), the 10-year BCFI was significantly improved with OFS: 76.6% in the TAM + OFS group vs. 65.7% in the TAM-only group (HR, 0.62; 95% CI, 0.40–0.98). This benefit was particularly pronounced in patients aged 40–45 years. Conclusions: We demonstrated the consistent benefit of adding OFS for 2 years to TAM in improving 10-year DFS. In patients with HR-positive/HER2-negative breast cancer and a high composite risk score, the addition of TAM plus OFS resulted in a 10.9% improvement in the 10-year BCFI, suggesting this approach may be beneficial, especially for those aged 40-45 years.