Abstract PS4-10-26: Pretreatment neutrophil-to-lymphocyte ratio is associated with pathologic complete response following neoadjuvant chemo-immunotherapy in early triple-negative breast cancer

Abstract Background: Neoadjuvant immunotherapy with chemotherapy is widely used for management of localized triple negative breast cancer (TNBC). While tumor infiltrating lymphocyte (TILs) have been associated with therapy response, the impact of absolute lymphocyte count (ALC) and neutrophil-to-lymphocyte ratios (NLR) in modulating response is not known. In this study, we evaluated the association between ALC, NLR, and therapeutic response to chemo-immunotherapy in patients with TNBC. Methods: In this multi-institutional retrospective study, patients with stage I-III TNBC diagnosed between 2019 to 2023 were included who were treated with at least one cycle of neoadjuvant pembrolizumab and chemotherapy at two comprehensive cancer centers. Pre-treatment laboratory values were collected for all patients. An NLR cut-off value of 5 was used based on previous studies. Univariate and multivariate logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on pCR. Results: A total of 372 patients with early-stage TNBC were included with an overall pCR rate of 61.3%. The median baseline NLR was 2.21 (95% CI, 2.10-2.30), and 9.4% of patients had a baseline NLR 5. Patients with a baseline NLR 5 had significantly lower pCR rates compared to those with NLR 5 (45.7% vs. 62.9%; p=0.047). Similarly, baseline lymphopenia was also associated with lower pCR rates (45.9% vs. 63.0%; p=0.043). Multivariate logistic regression demonstrated that baseline NLR 5 was significantly associated with inferior pCR rates (odds ratio OR, 0.49; 95% CI 0.24-0.997; p=0.049), adjusting for age, race and stage. Conclusions: This is the first study to demonstrate that absolute (and relative) lymphopenia is associated with lower pCR rates in patients with early-stage TNBC treated with neoadjuvant chemo-immunotherapy. Further research is needed to further evaluate lymphocyte count as a biomarker of neoadjuvant chemo-immunotherapy response and develop potential therapeutic strategies to improve lymphopenia in patients with early-stage TNBC. Citation Format: A. LeVee, E. Yang, K. Tsai, N. Baclig, A. Soliman, S. Zhang, A. Kordic, J. Mortimer, M. Lechner, S. Alkassis, N. McAndrew, M. Lipsyc-Sharf, M. Sedrak, R. Callahan, A. Master, D. Prager, K. McCann, A. Bardia. Pretreatment neutrophil-to-lymphocyte ratio is associated with pathologic complete response following neoadjuvant chemo-immunotherapy in early triple-negative breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-10-26.