Post-Neoadjuvant Chemotherapy Axillary Ultrasound in cN+ Breast Cancer: Can It Reliably Support de-Escalation of Axillary Surgery?

Background: Neoadjuvant chemotherapy (NAC) in up to 40%-60% of node-positive (cN+) breast cancer patients allows nodal pathological complete response, particularly in Her2+ and triple-negative subtypes. Accurate post-NAC axillary restaging is therefore critical to identify candidates for surgical de-escalation. Axillary ultrasound (AUS) remains the most widely used tool, but prior studies report highly variable performance, with false-negative rates approaching 25%, raising concerns about its reliability as a standalone guide. Methods: We retrospectively evaluated 413 patients with biopsy-proven cN+ breast cancer treated with NAC (2000-2024). All underwent AUS before surgery. AUS results (ycN0 vs. ycN+) were compared with final pathology (ypN0 vs. ypN+). Diagnostic performance was assessed, and predictors of false-negative AUS were identified using logistic regression. Results: AUS classified 51.6% of patients as ycN0, whereas only 45% achieved nodal pathologic complete response. Overall, AUS demonstrated 68% sensitivity, 76% specificity, 72% accuracy, positive predictive value 78%, and negative predictive value 66%. Performance differed by subtype: accuracy was highest in ER-/Her2 tumors (75%), but markedly lower in Her2+ (69%) and lobular carcinoma (67%). On multivariate analysis, absence of breast clinical complete response (OR 2.38, 95% CI [1.14-4.93]) independently predicted false-negative AUS findings. Conclusions: AUS following NAC provides only moderate accuracy, with a clinically relevant risk in patients lacking breast response. AUS alone should not determine omission of axillary surgery. A multimodal, biology-informed strategy combining AUS with other imaging techniques is needed to safely guide axillary de-escalation and minimize both overtreatment and undertreatment.