Adjuvant endocrine treatment strategies for non-metastatic breast cancer: a network meta-analysis.

Background: Multiple trials have evaluated escalation strategies of endocrine therapy for early breast cancer, including ovarian function suppression (OFS) and aromatase inhibitors (AI) in premenopausal patients and extended endocrine therapy. However, several aspects remain controversial due to the heterogeneity of study designs and lack of statistical power in relevant subgroups. We aimed to investigate the optimal endocrine therapy strategy. Methods: A systematic literature search was performed and last updated in August 2024 to identify randomized controlled trials (RCT) evaluating endocrine treatment strategies for hormone receptor positive breast cancer. A network meta-analysis with a frequentist framework using random-effects model was used to pool direct and indirect evidence. In addition, an extracted individual patient data meta-analysis was conducted to estimate the absolute differences between treatments. Study endpoints were disease-free survival (DFS), overall survival (OS), and safety. PROSPERO: CRD42023447979. Findings: A total of 37 RCT that had enrolled 107,684 patients were included in the study. During the first five years, OFS + AI was the most effective strategy in premenopausal women, while AI or switch strategy showed the better efficacy results in postmenopausal ones. Following five years of tamoxifen, continuation with five additional years of AI was associated with improved 8-year DFS (85.8%) compared to no extended therapy (78.1%) or five additional years of tamoxifen (81.0%). Following five years of AI or switch strategy, extended treatment with AI improved DFS (Hazard Ratio = 0.81, 95% Confidence Interval 0.73-0.90). Interpretation: This study provides information regarding the optimal endocrine treatment strategies for patients with resected hormone receptor positive early breast cancer. Funding: None.