Can Contrast-Enhanced Ultrasound Reduce the False-Negative Rate of Metastatic Axillary Lymph Nodes After Neoadjuvant Therapy in Breast Cancer?

Background: Accurate assessment of axillary lymph node (ALN) status after neoadjuvant therapy (NAT) remains essential for surgical planning in patients with initially node-positive breast cancer. This study evaluated the potential value of contrast-enhanced ultrasound (CEUS) in conjunction with sentinel lymph node biopsy (SLNB) for post-NAT axillary assessment and explored clinicopathologic factors associated with lymph node (LN) status. Methods: In this retrospective study, 179 patients with cytologically confirmed node-positive breast cancer underwent CEUS after NAT, followed by surgical pathological evaluation. The observed false-negative rate (FNR) of post-NAT CEUS combined with SLNB was compared with that of SLNB alone and post-NAT ultrasound (US) combined with SLNB. Univariable and multivariable generalized estimating equation (GEE) analyses were performed to identify factors associated with LN-level outcomes. Results: A total of 213 sentinel lymph nodes were analyzed. CEUS combined with SLNB had an observed FNR of 13.25% (95% CI, 7.56–22.19%), which was numerically lower than the FNRs of SLNB alone and US combined with SLNB. HER2 status, hormone receptor status, breast pathological response after NAT, and CEUS findings were significantly associated with nodal status in the univariable GEE model. Exploratory multivariable GEE analyses identified pre-NAT HER2 positivity as an independent protective factor for false-negative LN outcomes, whereas pre-NAT ER status and residual invasive carcinoma were independently associated with CEUS-negative/SLNB-positive nodal status. The exploratory models showed high apparent discrimination, with AUCs of 0.941 (95% CI, 0.890–0.991) and 0.917 (95% CI, 0.866–0.968). Conclusions: In this single-center retrospective cohort, the addition of post-NAT CEUS to SLNB was associated with a lower observed FNR than SLNB alone. These findings support the potential role of CEUS as a complementary tool for post-NAT axillary assessment but require prospective studies with external validation.