Predictors of Response to Neoadjuvant Systemic Therapy and Survival in Patients with cN1 Breast Cancer

BACKGROUND: Patients with clinically node-positive (cN1) breast cancer represent a heterogeneous population with evolving axillary management strategies. We evaluated whether extent of axillary nodal involvement is associated with survival in cN1 disease. METHODS: A retrospective study of patients with cT1-4N1M0 breast cancer and biopsy-proven axillary metastasis (2012-2018) was performed. All patients underwent axillary ultrasound (AUS) prior to neoadjuvant systemic therapy (NST) and again before surgery. Kaplan-Meier method and multivariable Cox proportional hazards models were used for statistical analysis. RESULTS: Among 825 patients, most had cT2-3 (75.6%), hormone receptor-positive/HER2-negative (HR+/HER2-; 73%), ductal (89.7%) carcinoma. 64.1% (529) had 1-3 abnormal nodes on pretreatment AUS, whereas 35.9% had > 3 abnormal nodes. Definitive axillary surgery consisted of axillary lymph node dissection in 83.3% and sentinel node biopsy or targeted axillary dissection in 16.7%. Pathologic complete response (pCR) rate (breast and nodes) was 22.7%; breast-only and nodal-only pCR rates were 6.4% and 11.8%, respectively. At median follow-up of 5.6 years, 5-year overall survival, breast cancer-specific survival, and event-free survival were 92%, 94%, and 91%, respectively. Overall (breast and nodes), nodal-only, and breast-only pCR were prognostic across all survival outcomes. On multivariable analysis, age, triple negative subtype, cT4 tumors, lack of pCR, and > 3 abnormal nodes on pretreatment AUS were independent predictors of worse outcomes. CONCLUSIONS: Among patients with cN1 breast cancer receiving NST and surgery, long-term survival outcomes were excellent. Extent of pretreatment nodal involvement by AUS was prognostic and could help to determine treatment selection in patients with cN1 disease.