Abstract PS6-45: Prognostic significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with breast cancer receivingneoadjuvant chemotherapy
Authors: García-Torralba Esmeralda , Ayala de la Peña Francisco , Alvarez-Abril Beatriz , de la Morena Barrio Pilar , Rubio Alejandra Ivars , Garre Elisa Garcia , Zafra Gema Marin , Carmona-Bayonas Alberto , Martinez Elena Garcia 
Published: February 2021

Abstract
Introduction and objectives: Tumor infiltrating lymphocytes (TILs) and neutrophil-to-lymphocyte ratio (NLR) play a prognostic role in early stage breast cancer (BC). There is no evidence about the combined effect of both factors. Our objective was to evaluate the integrated clinical significance of TILs and NLR in patients with early BC treated with neoadjuvant therapy. Materials and methods: Retrospective, single-center analysis of a cohort of patients with early BC treated with neoadjuvant chemotherapy between 2001-2010. Pre-treatment TILs (CD3+-TIL count) was evaluated using a tumor tissue microarray. NLR was calculated within one month of cancer diagnosis. TILs (logarithmic transformed) and NLR were analyzed as continuous variables. Survival analysis was performed using multivariable Cox regression models. Results:A total of 121 patients were included. Median age: 56 years. Cancer stage at diagnosis: 16% IIA, 28% IIB, 33% IIIA, 7% IIIB and 16% IIIC. Molecular subtype: 64% hormone receptor(HR)-positive (12% HER2-positive), 11% HER2-positive HR-negative and 22% triple-negative. Pathological complete response (pCR): 16.5%. Median follow-up: 12 years. Pre-treatment TIL analysis was available in 71 patients (59%) and NLR in 101 (83%). There was no correlation between both variables (Spearman's Rho: 0.03, p = 0.98). In the univariate analysis, the NLR showed a negative prognostic value for overall survival (OS) (HR 1.23, 95%CI 1.11-1.36; p &lt;0.001, C-index: 0.64 95%CI 0.52-0.77, p = 0.69). The effect was opposite for TILs (HR: 0.76 95%CI 0.61-0.95, p = 0.02; C-index: 0.69 95%CI 0.57-0.81, p = 0.69). The linear approximation was adequate, and there was no suspicion of non-proportionality of the hazards. In the multivariate analysis, including or not cancer staging after neoadjuvant therapy, NLR remained as an independent variable (HR 1.18, 95%CI 1.04-1.33; p = 0.01) and a statistic trend for TILs was also observed (HR 0.83, 95%CI 0.65-1.07; p = 0.16). Given the limited sample size, the multivariate analysis did not provide clear evidence of an additive effect. Nevertheless, the combined analysis of both parameters showed a better fit with respect to the two variables separately (Akaike Information Criterion for the combined model, for TILs and for NLR: 106, 133 and 214, respectively). Conclusion:The integrated characterization of TILs and NLR identifies different prognostic subgroups in early BC patients receiving neoadjuvant chemotherapy. Future validation of these findings in large, multicenter cohorts might allow treatment optimization by means of new strategies such as immunotherapy.
Citation Format: Esmeralda García-Torralba, Francisco Ayala de la Peña, Beatriz Alvarez-Abril, Pilar de la Morena Barrio, Alejandra Ivars Rubio, Elisa Garcia Garre, Gema Marin Zafra, Alberto Carmona-Bayonas, Elena Garcia Martinez. Prognostic significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with breast cancer receivingneoadjuvant chemotherapy [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-45.