Surgical axillary intervention after neoadjuvant systemic therapy (NST) for early-stage breast cancer – Clinical significance of micrometastases: Data from five neoadjuvant studies

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INTRODUCTION: Axillary surgery for early breast cancer has become less aggressive. However, the optimal approach after neoadjuvant systemic therapy (NST) remains uncertain and depends on axillary response. Especially the significance of nodal micrometastases (ypN1mi) after NST regarding oncological outcome remains controversial. Our study retrospectively analyzed ypN1mi occurrence in five neoadjuvant GBG/AGO-B trials from 2012 to 2019. METHODS: We analyzed 3211 high-risk early breast cancer patients from five neoadjuvant chemotherapy studies (GeparSepto, GeparOcto, GeparNuevo, GeparX, GeparOla). Patients who underwent breast surgery were analyzed based on type of axillary surgery, ypN1mi incidence, and its correlation with outcome. RESULTS: 98.5% (3163/3211) of patients had breast surgery and axillary information data available. Before NST, 44.1% (1395/3163) had sentinel lymph node biopsy (SLNB), 0.7% (22/3163) underwent axillary lymph node dissection (ALND), and 55.2% (1746/3163) had no axillary surgery. After NST, 65.3% (2057/3150) underwent axillary surgery: SLNB only in 19.4% (612/3150), targeted lymph node biopsy (TLNB) only in 0.2% (5/3150), targeted axillary dissection (TAD) in 0.9% (27/3150), ALND only in 40.9% (1288/3150), and completion ALND following SLNB, TLNB, or TAD in 4.0% (125/3150). Disease-free survival (DFS) was significantly reduced with hazard ratios (HR) of 2.53 (CI 1.63-3.92; p < 0.001) for ypN1mi and 2.43 (CI 1.98-3.00; p < 0.001) for ypN1 compared to ypN0. Likewise, HRs for overall survival (OS) were 3.17 (CI 1.77-5.68) for ypN1mi and 3.03 (CI 2.28-4.03) for ypN1. CONCLUSION: Our data suggest that minimal axillary residuals after NST may affect DFS, DDFS and OS; however, further analysis is needed to assess other variables.

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