Abstract Background: The optimal axillary management for breast cancer patients achieving nodal pathological complete response (ypN0) after neoadjuvant therapy (NAT) remains unclear, particularly regarding the use of sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND). We aimed to compare survival outcomes associated with SLNB and ALND in ypN0 patients and evaluate the influence of clinical nodal stage and postoperative axillary radiotherapy. Methods: Using the National Cancer Database (2018-2022), we identified female patients with clinical stage I-III invasive breast cancer who received NAT and achieved ypN0. Patients were grouped based on receipt of SLNB or upfront ALND. Overlap weighting using propensity scores was applied to adjust for baseline differences. Overall survival (OS) was compared using Kaplan-Meier analysis and Cox proportional hazards modeling. Subgroup analyses were stratified by initial clinical nodal stage (cN0-cN3), and exploratory analyses evaluated the impact of axillary radiotherapy on OS. Results: Among 36,452 eligible ypN0 patients, 86.3% received SLNB and 13.7% underwent ALND. After weighting, covariate balance was achieved. SLNB was associated with improved OS compared to ALND (weighted HR: 1.33; 95% CI: 1.11-1.60; p=0.03). Survival benefit from SLNB was strongest in cN0 (HR: 0.65; 95% CI: 0.47-0.89) and cN1 (HR: 0.67; 95% CI: 0.52-0.87) subgroups. No significant OS difference was observed in cN2 or cN3 patients. Axillary radiotherapy did not significantly influence OS in either SLNB or ALND groups. Conclusions: In breast cancer patients achieving ypN0 after NAT, SLNB is associated with favorable survival compared to ALND, particularly in those with low baseline nodal burden (cN0-cN1). The lack of OS benefit from axillary radiotherapy suggests that de-escalation strategies may be safe and appropriate in selected patients. These findings support individualized, response-adapted axillary management after NAT. Citation Format: Q. Shang, Z. Yan, L. Sheng, W. Xin. Axillary Management Strategies in Breast Cancer Patients With ypN0 After Neoadjuvant Therapy abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-11-09.
Shang et al. (Tue,) studied this question.