Nodal Pathologic Response to Neoadjuvant Systemic Therapy in Clinical N2 and N3 Nonmetastatic Breast Cancer

Axillary lymph node dissection is recommended for patients with clinical nodal stage 2-3 (cN2/cN3) breast cancer following neoadjuvant systemic therapy (NST), although some achieve nodal pathologic complete response (ypN0) and may be candidates for surgical de-escalation. Nodal response in this population is not well defined. We aimed to determine the frequency of ypN0 and identify clinicopathologic factors associated with nodal response.

A retrospective cohort study of our institutional cancer registry (2018-2024) included women with clinical T1-T4, N2-N3, and no distant metastasis breast cancer who received NST followed by axillary lymph node dissection. We determined the proportion of patients who achieved ypN0 and compared demographic, clinical, and tumor characteristics between ypN0 and ypN + groups.

From 8948 patients with breast cancer, 133 had cN2-cN3 disease and 37 met the inclusion criteria. A total of 15 patients (40.5%) achieved ypN0 after NST, whereas 22 (59.5%) had residual nodal disease. Human epidermal growth factor receptor 2-positive tumors had the highest rate of ypN0 (P = 0.026). Breast pathologic complete response (ypT0) was strongly associated with nodal response: 66.7% of ypN0 patients achieved ypT0 compared with 4.5% of ypN + patients (P < 0.001). Other demographic and clinical features were similar between groups.

Over 40% of patients with cN2/cN3 disease achieved ypN0 after NST. Residual nodal disease was more common in human epidermal growth factor receptor 2 -negative tumors and in patients without ypT0, and younger age showed a trend toward improved nodal response. These factors may help guide individualized consideration of axillary surgical de-escalation in selected patients.