Axillary Management in Clinically Node-Positive (cN1) Estrogen Receptor-Positive Breast Cancer

Background/Objectives: Axillary management in breast cancer continues to de-escalate, with trials showing similar outcomes between sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) in clinically node-negative patients. However, equivalence has not been demonstrated in estrogen receptor-positive (ER+), clinically node-positive (cN1) patients. We hypothesize that SLNB would not be associated with inferior outcomes compared to ALND among this population. Methods: Using the TriNetX Network, we identified women aged ≥18 years with cN1, ER+ breast cancer who underwent axillary surgery, inclusive of both upfront surgery and neoadjuvant-treated patients. Stage IV disease was excluded. The index event was the first axillary surgery (SLNB or ALND). Propensity score matching (1:1) was performed, balancing for age, receptor status, tumor characteristics, treatment, surgical procedure, and comorbidities. Outcomes included overall survival (OS) and local recurrence (LR). Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using Cox models. Results: A total of 1162 women were identified (SLNB 641, ALND 521). After matching, 435 patients remained in each cohort. At up to 10 years, OS was similar between groups (77% vs. 76%, HR 0.9, 95% CI 0.66–1.27). Breast recurrence occurred in 5% versus 7% (HR 0.82, 95% CI 0.47–1.42). Axillary recurrence occurred in 21% versus 24% (HR 0.9, 95% CI 0.69–1.21). None of these differences reached statistical significance. Conclusions: In ER+, cN1 node-positive breast cancer, SLNB was not associated with worse survival or recurrence compared with ALND. These real-world findings are hypothesis-generating but support the continued investigation and refinement of axillary de-escalation guidelines for clinically node-positive disease.