Supplementary Material for: Effectiveness of Hormonal Therapy for Post-Menopausal Women with Hormone Receptor-Positive Advanced Breast Cancer: A Systematic Review and Meta-Analysis of Clinical Trials

Objective: Breast cancer (BC) cells exhibit mutations over time, conferring resistance to therapeutic approaches. We attempted to ascertain the efficacy of selected hormonal therapy for advanced BC. Methods: This is a systematic review and meta-analysis of clinical trials. We searched Medline, PubMed, Cochrane Library, Web of Science and others. Studies that investigated the effectiveness of hormonal therapy for HR+ advanced BC were included. The outcomes were progression-free survival (PFS), overall survival (OS) and objective response rate (ORR). A random-effect meta-analysis model was employed. The study protocol was registered with the International Prospective Register of Systematic Reviews: CRD42023431939. Results: 21 studies were included in the meta-analysis with an overall sample size of 8482. ORR and PFS between aromatase inhibitors (AI) and other hormonal therapies: selective estrogen receptor degrader (SERD), selective estrogen modulator (SERM) and androgen inhibitors showed no significant difference [OR = 1.122 (0.917-1.374), p = 0.263]; [OR = 0.010 (0.000-1.292), p = 0.063], respectively. Sub-group analysis showed a statistically significant difference in ORR in favour of patients who received SERM compared to AI [OR = 1.362 (1.033-1.795), p = 0.028]. For OS, no significant difference was observed among anastrozole, letrozole and exemestane recepients [OR = 1.718 (0.021-139.128), p = 0.809]. Conclusion: Given the above findings, clinical decisions could be based on factors such as the line of cancer treatment, adverse events, drug dosing, and individual drug benefits. Although newer combination therapies are being adopted, the agents explored in this review are still widely used in clinical practice for HR+ BC.