Abstract 5698: Infiltrating immune cells in breast cancer subtypes
Authors: Matta Jaime L. , Encarnacion Jarline , Ortiz Carmen , Dutil Julie , Weber Amy , Pilon-Thomas Shari 
Published: August 2018

Abstract
In 2017, breast cancer (BC) affected around 29% of Hispanic women in the US according to the American Cancer Society. Among Hispanics, Puerto Rican women are one of the most diverse groups in terms of ancestry and culture. This diversity adds complexity to the BC etiology in this population. Several population studies have suggested ancestry as a BC risk factor which needs to be considered in clinical trial design aiming at selecting better therapies. In contrast to chemotherapeutic treatments known to have significant toxicities, some immunotherapies are recognized by having modest toxicity grades with a high capacity for individualized medicine. Monoclonal antibodies such as trastuzumab are used to treat BC by stratifying patients according to their molecular subtypes. Depending on whether BC tumors are (+) or (-) for the estrogen (ER), progesterone (PR), and HER2, four molecular subtypes have been identified: luminal A (ER+, PR+/−, HER2-), luminal B (ER+, PR+/−, HER2+), HER2+ (ER−, PR−, HER2+), and basal-like (ER−, PR−, HER2−). The objective of this study is to elucidate the distribution of molecular BC subtypes and ancestry markers in Puerto Rican women and to establish the relationship between these distributions with their tumor infiltrating lymphocytes (TIL). Our overall hypothesis is that Hispanic women with BC will have distinct molecular subtypes and ancestry distributions that will be associated with their TIL signature. By combining samples collected through the Puerto Rico Bio-Bank and from our BC cohort, 129 blood and tumor tissue samples were selected. Molecular BC subtypes were classified using PAM50. A panel of ancestry informative markers was genotyped on iPLEX technologies and global ancestry proportions were estimated using ADMIXTURE. PanCancer Immune Panel was used to characterize the TIL based on RNA signatures. The initial results obtained through PAM50, showed that 45% of the tumors were luminal A, 27% luminal B, 18% basal-like, and 7% HER2+. Global ancestry proportions for each patient grouped by PAM50 subtype were performed. Overall, the ancestry proportions were: 67% European (SD ± 12%), 19% African (SD ± 11%), and 14% Native American (SD ± 7%). To evaluate the TIL RNA signature among subtypes, a principal component analysis (PCA) was performed followed by an immune score using the PCA2. The PCA2 score was able to distinguish among the basal-like, luminal A and luminal B subtypes; however, the HER2+ samples could not be clearly distinguished from the luminal A or B subtypes. These results show a qualitative tendency intrinsic of each molecular BC subtype and the TIL signature. Long-term, this approach of studying BC subtypes, ancestry, and immune infiltrates while increasing sample size is expected to provide data needed to improve prognostic tools to support the design of immunotherapies for Hispanic women with BC. This study was supported by: #S06GM008239-20, 9SC1CA182846-04, #U54CA163068, 2U54CA163071-06, and R003050/MD007579.
Citation Format: Jaime L. Matta, Jarline Encarnacion, Carmen Ortiz, Julie Dutil, Amy Weber, Shari Pilon-Thomas. Infiltrating immune cells in breast cancer subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5698.