Abstract PR007: Tumoral infiltrating lymphocytes as a prognostic factor in triple negative breast cancer patients from Colombia
Authors: Huertas-Caro Carlos A. , Ramirez Mayra A. , Ballen Diego Felipe , Mejía Juan Carlos , Sua-Villegas Luz Fernanda , Cock-Rada Alicia , Zabaleta Jovanny , Fejerman Laura , Sanabria-Salas María Carolina , Serrano-Gomez Silvia J. 
Published: January 2023

Abstract
Introduction: Triple negative breast cancer (TNBC), occurs in 10%-20% of all breast cancer and presents a higher frequency in Latinas compared to non-Hispanic white women. It is highly immunogenic and high levels of tumor infiltrating lymphocytes (TILs) have been associated with a better overall survival and higher probability to achieve pathological complete response (pCR). Objective: This is the first study in Colombian women aimed to explore stromal TILs (sTILs) level and composition as a prognostic and predictive biomarker in TNBC. Methods: A total of 195 TNBC tumor biospecimens from patients diagnosed between 2008-2016 in 3 Colombian health institutions were included. Stromal TILs (sTILs) was evaluated following the recommendations of the International TILs Working Group 2014 in hematoxylin & eosin slides from pre-treatment samples. The number of positive cells for CD4 and CD8 was evaluated by immunohistochemistry and digital image capture. Parametric and non-parametric tests were used to evaluate differences in clinic-pathological characteristics according to sTILs levels and composition. Differences in overall survival were analyzed using Kaplan-Meier curves and the log-rank test. Cox regression analysis was used to analyze sTILs as a prognostic marker for overall survival. A logistic regression model was applied to evaluate the association of sTILs with pCR. Results: Tumors with high sTILs levels were more likely to be early stage (64.4% stage I/II) compared to tumors with low sTILs levels (35.5%). Additionally, when compared patients with high sTILs vs. low sTILs, a higher percentage of patients with high sTILs didn’t receive neoadjuvant chemotherapy (NAC) (high:50% vs. low:32.7%, p=0.025) and received more conservative surgeries (high:60% vs. low:37.9%, p&lt;0.05). Similar results were observed for patients with high CD4/8 infiltration. Longer overall survival times were observed in patients with high sTILs (84.9 mo vs. 41.4 mo, p&lt;0.05), as well as in patients with high CD4+ infiltration (p&lt;0.05) and CD8+ (p&lt;0.015). In the multivariate analysis, low levels of sTILs was found to be independent prognostic factor associated with a higher risk of death (HR: 1.59, 95% CI 1.01-2.48). Regarding sTILs as a predictive biomarker, a higher number of patients with high sTILs and high CD4+ cells achieved clinical complete response to NAC (sTILs: 28.6% vs. 9.3%, p=0.022; CD4: 29% vs 9.4%, p=0.032) and pCR (sTILs: 42.9% vs. 15.8%, p=0.023; for CD4: 43.3% vs 16.3%, p=0.006) compared to patients with low infiltration. Likewise, a statistically significant association between sTILs and pCR was observed (OR: High sTILs 1.486, 95% CI 1.14 - 2.013). Similar results were observed for high CD4 and CD8 infiltration (OR: 1.262, 95% CI 1.061 - 1.536, OR: 1.337, 1.085 - 1.694, respectively). Conclusions: Our results suggest that sTILs levels are a prognostic marker for overall survival and a predictive marker for pCR in TNBC patients from Colombia as has been reported in previous studies including biospecimens from mostly European ancestry patients.
Citation Format: Carlos A. Huertas-Caro, Mayra A. Ramirez, Diego Felipe Ballen, Juan Carlos Mejía, Luz Fernanda Sua-Villegas, Alicia Cock-Rada, Jovanny Zabaleta, Laura Fejerman, María Carolina Sanabria-Salas, Silvia J. Serrano-Gomez. Tumoral infiltrating lymphocytes as a prognostic factor in triple negative breast cancer patients from Colombia [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PR007.