Survival outcomes of axillary de-escalation following neoadjuvant chemo-immunotherapy in clinically node-positive triple-negative breast cancer: a national cancer database study

Background: Adding immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NAC) enhances systemic efficacy in triple-negative breast cancer (TNBC). However, its impact on the survival outcomes of axillary surgical de-escalation remains undefined. This study evaluates whether chemo-immunotherapy mitigates survival risks historically associated with omitting axillary lymph node dissection (ALND) for sentinel lymph node biopsy (SLNB) in clinically node-positive (cN+) disease. Methods: In this retrospective cohort study using the National Cancer Database (2018-2022), we identified women with cN1-3, cM0 TNBC who received NAC ± ICIs and achieved ypN0 (axillary pathological complete response), followed by axillary surgery (SLNB or ALND). Overall survival (OS) was evaluated using restricted mean survival time (RMST) and propensity score matching. Multivariable Cox models assessed the independent effect of surgical extent (SLNB vs. ALND) on OS. Results: Out of 1,315,170 breast cancer cases, 4,336 eligible patients were included. The therapeutic regimen significantly interacted with the survival impact of axillary de-escalation. With NAC alone, SLNB was independently associated with inferior OS compared to ALND [5-year OS: 83.0% vs. 87.8%, P = .027; adjusted hazard ratio (aHR)=1.63, 95% CI = 1.12-2.38, P = .01]. Strikingly, adding ICIs neutralized this disparity: in the NAC+ICI cohort, SLNB yielded OS comparable to ALND (5-year OS: 90.1% vs. 93.6%, P = .99; identical 48-month RMST), with no significant survival detriment in multivariable analysis (aHR=1.19, 95% CI = 0.54-2.61, P = .67). Conclusions: The enhanced systemic control conferred by ICIs appears to compensate for the reduced surgical clearance of the axilla when ALND is omitted, effectively mitigating the survival risks associated with omitting ALND in cN+ TNBC. These real-world findings suggest modern chemo-immunotherapy facilitates axillary de-escalation without compromising overall survival, establishing a compelling rationale for prospective clinical trials.