Omission of axillary surgery in early breast cancer with negative lymph nodes: a systematic review and meta-analysis of randomized clinical trials

Abstract Purpose To evaluate whether the omission of axillary surgery impacts clinical outcomes in patients with early-stage breast cancer and clinically negative lymph nodes. Methods We conducted a systematic review and meta-analysis of randomized clinical trials (RCTs) comparing no axillary surgery with standard axillary interventions (sentinel lymph node biopsy [SLNB] or axillary dissection [AD]). This study followed PRISMA guidelines and was registered in PROSPERO (CRD420250653779). Searches were conducted in PubMed, Web of Science, and Embase through June 2025. Outcomes assessed included overall survival (OS), disease-free survival (DFS), and axillary recurrence (AR). Meta-analyses were performed using RevMan 5.4. Risk of bias was assessed using the RoB 2 tool. Results Out of 853 records, seven RCTs including 8806 patients met the inclusion criteria. Among them, 2,915 patients underwent no axillary surgery, while 5891 received surgical axillary treatment. Two trials compared no surgery with SLNB, and five compared no surgery with AD. No significant differences were found in OS (OR = 1.02; 95% CI, 0.86–1.20; p = 0.84; I 2 = 36%) or DFS (OR = 0.80; 95% CI, 0.63–1.00; p = 0.05; I 2 = 63%). AR was significantly lower in the axillary surgery group (OR = 0.18; 95% CI, 0.10–0.31; p < 0.01; I 2 = 39%). Conclusion The omission of axillary surgery in early-stage breast cancer with clinically negative lymph nodes does not negatively impact overall or disease-free survival. However, it is associated with a higher—though still low—risk of axillary recurrence.