Abstract Background: Accurate axillary staging after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer remains controversial, particularly in settings where radioisotopes are unavailable. We prospectively evaluated the performance of single-blue-dye sentinel lymph node biopsy (SLNB) combined with clip-guided targeted axillary dissection (TAD). Methods: Consecutive patients with biopsy-proven cN1-2 disease received standard NAC. The biopsy-positive node was clipped prior to treatment. During surgery, 2-4 mL of methylene blue was injected peritumorally; all blue-stained nodes were resected as sentinel lymph nodes (SLNs), followed by selective excision of the clipped (marked) node. Completion axillary lymph node dissection was performed only in cases where residual nodal disease was identified. The primary endpoints were the SLN identification rate (IR), concordance of pathologic status between the marked lymph node (MLN) and SLNs, and the false-negative rate (FNR; negative SLNs with metastasis in non-SLNs). Results: Twenty-nine women (median age 48 years; range, 31-68 years) were enrolled between July 2022 and February 2024. SLNs were successfully identified in 28/29 patients, yielding an IR of 96.6% (95% CI 82.8-99.4). The MLN was retrieved as an SLN in 28/29 cases (96.6 %), and it constituted the first SLN removed in 19/28 (67.9 %). Residual nodal disease was present in 11/29 patients (37.9%). One of these 11 patients had negative SLNs but positive non-SLNs, leading to an overall FNR of 9.1% (1/11; 95% CI 0-41.3). Nodal pathological complete response (pCR) rates varied by molecular subtype: 90% in triple-negative tumors, 66.7 % in HER2-positive tumors, and 44.4 % in HR+/HER2-negative tumors. No dye-related adverse events were observed. Conclusions: The combination of single-blue-dye SLNB and clip-guided TAD demonstrated a high identification rate, excellent MLN-SLN concordance, and FNR below the 10% benchmark. This pragmatic and minimally invasive approach provides a reliable alternative to routine axillary lymph-node dissection in post-NAC patients when dual tracers or radioisotopes are unavailable. Citation Format: W. Chen, Y. Jini, P. Liwei, N. Chao, H. Jian. Single-dye sentinel lymph node mapping for targeted axillary dissection in breast cancer patients after neoadjuvant chemotherapy: a prospective study 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 PS2-05-04.
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