Abstract
BACKGROUND: The oncologic safety of breast-conserving surgery (BCS) compared with mastectomy in women with node-positive breast cancer remains uncertain in the modern era of systemic therapy and radiotherapy (RT). The aim of this study was to clarify the comparative survival and recurrence outcomes of BCS with RT versus mastectomy in women with pathologically confirmed node-positive breast cancer through a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: RCTs enrolling women with pathologically confirmed node-positive breast cancer and directly comparing BCS plus RT with mastectomy were systematically identified. Searches of PubMed, Embase, Web of Science, and Cochrane CENTRAL were conducted through May 2025, following PRISMA 2020 guidelines. Hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS), and breast cancer-specific survival (BCSS), and risk ratios (RRs) for locoregional recurrence (LRR) were pooled using random-effects models. Risk of bias was assessed with the Cochrane RoB 2.0 tool, and sensitivity analyses were conducted to evaluate robustness across trial eras and locoregional treatment strategies. RESULTS: Ten RCTs comprising 11,714 node-positive patients were included. All BCS patients received whole-breast irradiation (WBI), and nearly all participants received systemic therapy appropriate to tumor biology. Pooled analyses showed no significant differences between BCS and mastectomy for OS [HR 0.94, 95% confidence interval (CI): 0.81-1.07], DFS (HR 1.03, 95% CI: 0.93-1.12), BCSS (HR 1.00, 95% CI: 0.81-1.18), or LRR (RR 0.98, 95% CI: 0.81-1.16). Heterogeneity was negligible (I(2)=0% for all endpoints). Sensitivity analyses-including exclusion of individual studies, restriction to low-risk-of-bias trials, and stratification by trial era-confirmed the stability of results. Variations in axillary surgery (sentinel lymph node biopsy vs. axillary lymph node dissection) and RT fields (WBI alone vs. WBI + regional nodal irradiation) did not modify comparative outcomes. No publication bias was detected. CONCLUSIONS: BCS with RT provides survival and recurrence outcomes equivalent to mastectomy in women with node-positive breast cancer. These findings support BCS as a safe, patient-centered surgical option in the modern multimodality treatment era and provide a strong evidence base for harmonizing guidelines and reducing unnecessary radical surgery. Future trials incorporating molecular profiling and response-adapted strategies are warranted to refine patient selection.