Background: Sentinel lymph node (SLN) surgery after neoadjuvant chemotherapy (NAC) has been well studied. However, outcomes data addressing the oncologic safety of this technique are sparse. This study aimed to evaluate use of SLN surgery versus axillary lymph node dissection (ALND) for clinically node-positive patients treated with NAC and to report outcomes. Methods: The study identified patients at the authors’ institution with biopsy proven clinically node-positive (cN1–cN3) breast cancer undergoing axillary surgery after NAC from 2009 to 2019. Practice patterns and outcomes were evaluated. Results: Of 602 patients, 52.3% underwent SLN surgery. Use of SLN surgery increased significantly over time, reaching 75.3% during 2015–2019. For 52.5% of the patients who had an SLN identified, ALND was not used. Use of ALND (± SLN surgery) decreased from 100% in 2009 to 57.2% in 2015–2019. The nodal positivity rate of patients who proceeded directly to ALND was 64.5% (185/287), increasing significantly over time. Factors significantly associated with performing SLN surgery on multivariable analysis were lower presenting clinical T category, lower presenting clinical N category (cN1 vs cN2–3) and HER2-positive status. During the median 34-month follow-up period, 17 regional recurrences were observed (16/443 with ALND; 1/159 with SLN surgery alone), for a 2-year freedom-from-regional-recurrence rate of 99.1% among the SLN surgery patients and 96.4% among the ALND patients (p = 0.10). Conclusions: For cN1–3 breast cancer treated with NAC, SLN surgery has been incorporated into clinical practice at the authors’ institution. In this study, selection for SLN surgery was based on clinical factors and tumor biology. More than half of the patients who were selected for SLN surgery were spared ALND, with a low nodal failure rate and no recurrence-free survival disadvantage at 2 years.
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