Impact of Adjuvant Chemotherapy on Survival Outcomes in Intermediate‐ and High‐Risk ER+/HER2− Breast Cancer Stratified by Genomic Profiling: A Meta‐Analysis

Background Genomic recurrence score (RS) testing guides adjuvant treatment decisions in oestrogen receptor‐positive, HER2‐negative early breast cancer. Evidence remains mixed regarding the survival benefit of adding chemotherapy to endocrine therapy (CET) in intermediate‐ and high‐risk RS groups. This meta‐analysis assessed overall mortality, breast cancer‐specific mortality (BCSM) and recurrence outcomes according to RS category. Methods Medline, Embase, PubMed and Google Scholar were searched from 1 January to 20 June 2024 for studies reporting outcomes in ER+/HER2− patients treated with CET versus endocrine therapy (ET) alone, stratified by RS. Random‐effects modelling generated pooled risk ratios (RRs) with 95% confidence intervals (CIs). Heterogeneity was evaluated using I 2 , and risk of bias was assessed with ROBINS‐I. Results Fifteen studies comprising 630,741 patients were included. In the high‐risk group (RS > 25), CET significantly reduced 5‐year overall mortality compared with ET (5.9% vs. 7.9%; RR 0.57, 95% CI 0.45–0.72; I 2 = 91 % ). Node‐negative high‐risk patients also showed improved survival (RR 0.48, 95% CI 0.37–0.64; I 2 = 77 % ). BCSM was lower with CET in high‐risk patients (RR 0.81, 95% CI 0.67–0.97; I 2 = 0 % ). In the intermediate‐risk group (RS 11–25), CET did not significantly reduce overall mortality (RR 0.72, 95% CI 0.49–1.06; I 2 = 94 % ) or BCSM (RR 1.28, 95% CI 0.91–1.79; I 2 = 45 % ). Subgroup analysis of RS 16–25 showed lower overall mortality with CET (RR 0.48, 95% CI 0.42–0.55; I 2 = 0 % ), although BCSM was similar. Data for 5‐year recurrence outcomes were insufficient for pooled analysis. Conclusion Chemotherapy provides a clear survival benefit in high‐risk RS groups, including node‐negative patients, whereas intermediate‐risk groups show limited benefit. These findings support selective use of CET guided by genomic risk stratification.