Background: Triple-negative breast cancer (TNBC) is an aggressive form of the disease with limited treatment options and poor survival. A series of retrospective studies established the presence of tumor-infiltrating lymphocytes (TILs) in most primary breast cancers, the number of which affect the response rate to chemotherapy in both neoadjuvant and adjuvant treatment contexts. A subset of TNBC is highly immunogenic, and recent studies have shown that understanding the specific immune profiles of tumors has implications both for treatment and prognosis. Most studies have been conducted in samples of women of European origin, and little is known about the immune profile of TNBCs in Hispanic/Latinas. The specific goal of our study was to test the association between immune characteristics of TNBC from Colombian patients and genetic ancestry proportions, to determine if genetic ancestry could be a relevant factor in defining the immune characteristics of TNBC.

Methods: We obtained 41 TNBC tissues through collaboration with the National Cancer Institute in Colombia along with demographic and clinical information. Genetic ancestry was estimated with a panel of 106 ancestry informative markers and the program STRUCTURE. RNA was extracted from FFPE tissues, qualified using Agilent chips, and used for sequencing at the Translational Genomics Core at the Stanley S. Scott Cancer Center. Using the TNBCtype program we confirmed 33 samples as TNBC. The program xCell was used for cell-signature identification based on RNAseq data. We explored associations between genetic ancestry and scores obtained for different immune cell-types and an overall immune score using linear regression. We analyzed the association for the following specific cells: Th1 cells, Th2 cells, Treg, CD4 T cells, CD4 TEM, CD4 memory T cells, CD8 T cells, CD8 TCM, CD8 TEM, CD8 naive T cells, macrophages, macrophages M1, macrophages M2, and mast cells.

Results: The overall immune score was positively associated with the proportion of African ancestry (p=0.049). Interestingly, we observed that Indigenous American ancestry was inversely associated with the Treg cell score while African ancestry was positively associated with it. Levels of these regulatory cells have been correlated with prognosis in ER- and triple-negative disease. We also found that CD4 T cell and CD4 memory T-cell scores were positively associated with African ancestry (P=0.006 and P=0.049 respectively).

Conclusions: Our results suggest that genetic ancestry among Latina women from Colombia is associated with certain immune characteristics of breast cancer. We need to further test these associations in a larger sample to confirm the findings, obtain additional insights, and understand their implications for TNBC treatment and prognosis among Latin American women.

Citation Format: Valentina A. Zavala, Laura C. Carrasquilla, Silvia J. Serrano-Gomez, Maria C. Sanabria-Salas, Melody C. Baddoo, Jone Garai, Jovanny Zabaleta, Laura Fejerman. Immune characteristics of triple-negative breast cancer (TNBC) in Latin American women from Colombia [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C092.