Axillary Pathologic Complete Response as a Stronger Prognostic Marker than Breast pCR in Clinically Node-Positive Stage II-III Breast Cancer.

Abstract

BACKGROUND: Pathologic complete response (pCR) after neoadjuvant systemic therapy (NAST) predicts improved survival in breast cancer, but the relative prognostic value of breast versus axillary pCR in initially node-positive disease remains unclear. METHODS: We analyzed 455 patients with clinically node-positive stage II-III breast cancer treated with NAST (2010-2022). Patients were classified by breast-axilla response patterns: both-site pCR (n = 99), breast-only pCR (n = 24), axilla-only pCR (n = 117), and neither pCR (n = 215). The primary endpoint was invasive disease-free survival (IDFS); overall survival (OS) was secondary. Multivariable Cox models assessed prognostic associations adjusted for clinicopathologic covariates. RESULTS: Median follow-up was 57.2 months; 135 IDFS events, and 118 deaths occurred. In head-to-head analysis, axillary pCR showed numerically stronger prognostic associations than breast pCR (IDFS adjusted hazard ratio [aHR] 0.441 vs. 0.501; OS aHR 0.373 vs. 0.544). Compared with neither pCR, both-site pCR (IDFS aHR 0.217, 95% confidence interval [CI] 0.12-0.394) and pooled discordant response patterns achieving one-site pCR (aHR 0.464, 95% CI 0.304-0.709) demonstrated favorable outcomes, whereas breast-only pCR, observed in small, underpowered subgroup (n = 24), did not show a statistically significant benefit (aHR 0.928, P = 0.849). Five-year IDFS was 89% (both-site pCR), 77% (axilla-only pCR), 65% (breast-only pCR), and 63% (neither pCR). Findings remained robust in sensitivity analyses restricted to biopsy-confirmed node-positive patients and ALND-only subsets. CONCLUSIONS: In clinically node-positive breast cancer treated with NAST, axillary pCR showed numerically stronger prognostic associations than breast pCR, although this apparent difference should be interpreted cautiously. Post-neoadjuvant nodal status may help to refine risk stratification and inform adjuvant treatment planning.