Neoadjuvant systemic therapy for triple-negative breast cancer: A safety-net health system’s experience.

e13127 Background: Pembrolizumab-based neoadjuvant chemoimmunotherapy has become a standard of care for stage II–III triple-negative breast cancer (TNBC) based on randomized trial data showing significant improved pathologic complete response (pCR) and survival compared to chemotherapy alone. These associations have yet to be studied within our large safety-net health system. We evaluated pCR and survival outcomes of neoadjuvant and surgery-first approaches at a single institution. Methods: This retrospective study included patients diagnosed with stage II–III TNBC at JPS Health Network between 01/01/2019 and 12/31/2024. Patients were stratified by initial treatment strategy into neoadjuvant therapy (NAT) and surgery-first groups. Within the NAT group, patients received either chemotherapy alone or pembrolizumab-based chemoimmunotherapy. The study end points were pCR, overall survival (OS), and disease-free survival (DFS). Associations between treatment regimen and pCR were assessed using logistic regression, while OS and DFS were estimated using Kaplan–Meier methods and compared by log-rank testing. Results: A total of 110 patients were included, with 94 receiving NAT and 16 treated with upfront surgery. Patients in the NAT group had more advanced disease, including a higher proportion of stage III diagnoses (42%), whereas 75% of surgery-first patients were diagnosed with stage IIA disease. Among 87 NAT patients who underwent definitive surgery, pCR rates differed significantly by regimen. Pembrolizumab-based chemoimmunotherapy accounted for 74% of all pCRs (p = 0.001). Pembrolizumab-based therapy was also the only regimen independently associated with pCR when compared with other chemotherapy-only regimens (OR 3.40; p = 0.03). Among patients who achieved pCR, 89% remained disease-free compared with 56% of those with residual disease. Failure to achieve pCR was associated with increased mortality risk (HR 1.88; 95% CI 1.13–3.13; p = 0.014). No statistically significant differences in OS or DFS were observed between the two treatment strategies or across neoadjuvant regimens. Conclusions: Pembrolizumab-based neoadjuvant chemoimmunotherapy was associated with significantly higher rates of pCR compared with other neoadjuvant regimens, despite more advanced disease at presentation. Achievement of pCR was strongly prognostic and associated with a lower mortality risk. Although survival differences by treatment strategy were not observed, likely due to limited follow-up and sample size, these findings highlight pCR as a primary end point and support the use of pembrolizumab-based neoadjuvant therapy in this safety-net setting.