Impact of neoadjuvant immunotherapy on safety of axillary de-escalation in triple-negative breast cancer (TNBC): A propensity score–matched analysis.

Abstract

e12674 Background: While the addition of immune checkpoint inhibitors (ICIs) to neoadjuvant chemotherapy (NAC) has improved systemic control and pathologic complete response in TNBC, its effect on de-escalation of axillary surgery and associated overall survival remains unclear. We investigated whether the addition of ICIs to NAC facilitates safe de-escalation of axillary lymph node dissection (ALND) to sentinel lymph node biopsy (SLNB) in patients presenting with clinically node-positive (cLN+) disease. Methods: Women > 18y cN1-3, cM0 TNBC diagnosed 2018-2022 were identified from the National Cancer Database. Patients were stratified by systemic therapy (NAC vs NAC+ICIs) and surgical procedure (SLNB vs ALND). Propensity score matching (PSM) and restricted mean survival time (RMST, truncated at 48 months) were utilized to assess overall survival (OS). Results: 4336 patients were included for analysis (cN1 = 3658 [84.4%], cN2 = 321 [7.4%], cN3 = 357 [8.2%]). NAC+ICI was associated with improved OS in the SLNB group (RMST 46.6 vs 46.1 mos, p = 0.03) but not the ALND group (RMST 46.4 vs 46.3, p = 0.91). In the NAC-alone cohort, SLNB was associated with significantly inferior survival vs ALND (5-year OS ALND 87.8% vs SLNB 83.0%, p = 0.027) and was independently associated with increased risk of mortality (HR 1.63, 95% CI 1.12–2.38, p = 0.01). Notably, in the NAC+ICI cohort, this survival difference did not persist, with SLNB and ALND having comparable survival (5-year OS ALND 93.6% vs SLNB 90.1%, p = 0.99) and identical 48-month RMSTs (46.4 months). Multivariable analysis confirmed that SLNB was not associated with worse survival in the immunotherapy setting (HR 1.19, 95% CI 0.54–2.61, p = 0.67). Conclusions: Among SLNB recipients, ICIs were associated with improved unadjusted OS, but this benefit was not observed among ALND recipients, suggesting the burden of axillary disease necessitating ALND aligns with overall worse prognosis and was less affected by ICI receipt. Patients receiving SLNB after NAC-alone had worse survival vs those receiving ALND, but it is unclear whether this survival difference is due to omission of axillary clearance or patient-level factors associated with the decision to omit ICIs in the first place (e.g., co-morbidities that might also have led to omission of ALND). Notable, however, among those receiving both NAC and ICIs, survival was comparable between SLNB and ALND recipients, suggesting ICIs safely facilitate axillary de-escalation and effectively control tumor burden without the need for axillary clearance beyond SLNB.