Abstract PR06: Differences in tumor-infiltrating lymphocytes between racially distinct triple-negative breast tumors
Authors: Wright Nikita , Lee Chaeyun , Guanhao Wei , Krishnamurti Uma , Li Xiaoxian , Rida Padmashree C.G. , Osan Remus , Aneja Ritu 
Published: February 2019

Triple-negative breast cancer (TNBC) is a highly aggressive breast cancer subtype that lacks hormone receptors [estrogen receptor (ER), progesterone receptor (PR)] and overexpression of human epidermal growth factor receptor 2 (HER2/neu). The disease is characterized by an aggressive clinical disease course, and a high risk of disease progression within 5 years of diagnosis. There are currently no targeted treatments available for TNBC, and surgery and chemotherapy are the mainstay of TNBC treatment. TNBC afflicts African-American (AA) women at a 2-3 times higher rate than European-American (EA) women. AAs also present with more aggressive clinicopathologic characteristics such as higher grade and stage at diagnosis, and experience poorer clinical outcomes than EAs among TNBC patients. Furthermore, AAs harbor more aggressive TNBC subtypes such as a basal-like phenotype and quadruple-negative [androgen receptor (AR)-negative TNBC] breast cancer than EA TNBC patients. This disparate burden underscores an urgent need to identify distinctions in inherent tumor biology between racially distinct TNBCs. Tumor-infiltrating lymphocytes (TILs) are implicated in killing tumor cells and thus have been associated with better clinical outcomes and response to neoadjuvant chemotherapy. Studies have also reported that TILs are associated with more aggressive clinicopathologic characteristics such as such as higher grade, stage, Ki67, TNBC status, and increased lymph node metastasis. In formalin-fixed, paraffin-embedded resection samples from TNBC patients who received adjuvant chemotherapy at Emory Hospital in Atlanta, GA, we compared overall (intratumoral and peripheral) TIL counts between AA and EA patients (n=121). We observed a trend of more TILs among AA (n=87) compared to EA (n=34) TNBC patients (p=0.02). Among early-stage (I-II) TNBC patients, we found that AAs (n=71) harbored significantly more TILs than EAs (n=32) (p=0.019) but not among late-stage (III-IV) patients (p=0.86). Among early-stage AA TNBC patients, more TILs negatively correlated with younger age at diagnosis (ρ=-0.25; p=0.03) and positively correlated with intramammary lymph node involvement (ρ=0.36; p=0.002). Furthermore, TILs correlated negatively with AR expression (ρ=-0.25; p=0.04) and positively with BRCA1-associated protein (ρ=0.3; p=0.02) and programmed cell death protein 1 (ρ=0.56; p&lt;0.0001) expression. Interestingly, we stratified peripheral TILs into high (≥10) and low (&lt;10) subgroups and discovered that high peripheral TILs were associated with better 10-year survival among early-stage AA TNBC patients (p=0.0389) but not among early-stage EA TNBC patients. Our findings uncover a previously unrecognized disparity in tumor microenvironment between AA and EA TNBC patients. Our results also suggest that TILs may serve as a prognostic biomarker that can stratify early-stage AA TNBC patients into high- and low-risk groups and allow for optimization of treatment paths. Further investigation into disparities in the immune landscape or tumor microenvironment among AA and EA TNBCs may yield promising new biomarkers and therapeutic targets for TNBC patients of African ancestry.

Citation Format: Nikita Wright, Chaeyun Lee, Wei Guanhao, Uma Krishnamurti, Xiaoxian Li, Padmashree C. G. Rida, Remus Osan, Ritu Aneja. Differences in tumor-infiltrating lymphocytes between racially distinct triple-negative breast tumors [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr PR06.