Abstract 2525: Understanding triple-negative breast cancer immune microenvironment by disease stages, obesity, and race
Authors: Hossain Fokhrul , Danos Denise , Zabaleta Jovanny , Wu Jiande , Lynch Mary Anne , Del Valle Luis , Wu Xiao-Cheng , Ochoa Augusto , Hicks Chindo , Miele Lucio 
Published: June 2022

Background: Triple-negative breast cancer (TNBC) is a molecularly heterogeneous group of clinically aggressive malignancies. There are well-recognized health disparities in TNBC outcomes, and the risk of TNBC is higher among African-Americans (AA). It is unclear whether immunological features of the tumor microenvironment (TME) associated with disease stage, socioeconomic factors, or comorbidities such as obesity may affect tumor immunity. The incidence of TNBC and obesity in Louisiana is among the highest in the nation, and we have documented disparities in incidence linked to race and disparities in mortality linked to social determinants of health. Recent studies described immunologic characteristics of the TNBC TME. However, the possible association of immunogenomic portraits of TNBCs with race, comorbidities or socioeconomic factors remains understudied.

Methods: We studied the expression of immunity-associated genes in clinically annotated TNBCs from Louisiana AA and European-American (EA) patients with or without obesity. Primary invasive breast cancer cases with confirmed TNBC diagnosis were identified by the Louisiana Tumor Registry (LTR). Sections of FFPE tissue containing ≥ 50% tumor were identified and processed for RNA-Sequencing [(n = 256; White women:125 (Lean: 50 and Obese:75) and Black women:131 (Lean:28 and Obese: 103)] at Translational Genomic Core, LSUHSC. Categorical outcomes were compared via Chi-squared tests, and survival was compared via log-rank tests. Spearman correlation analysis was used to determine associations between CIBERSORT cell populations and stage of disease at diagnosis.

Results: We found that race was associated with the stage of TNBC, and AA patients were more often diagnosed with a later stage of TNBC (p=0.0447). However, race was not associated with survival (p=0.4673). Obesity was not associated with stage at diagnosis (p=0.7256). Stage at diagnosis was the strongest determinant of survival (p&lt;0.0001). We utilized CIBERSORT analysis to identify and quantify immune cell populations within the TME. Later stage at diagnosis was associated with increased T follicular helper cells (p=0.0038), M1 macrophages (p= 0.0032), and activated mast cells (p=0.0487). Conversely, later stage of disease was associated with decreased resting mast cells (p=0.0004) and monocytes (p=0.0455). Immunosuppressive Treg cells were positively associated with stage at diagnosis in AA patients (p=0.0273) but not in EA patients (p=0.9141).

Conclusions: Stage at diagnosis was the strongest determinant of survival and was associated with significant differences in TME immune cell populations. Stage, race and obesity were associated with the presence of immunosuppressive Treg cells. If confirmed, these findings may help understand the variability in immunotherapy responses in TNBC.

Citation Format: Fokhrul Hossain, Denise Danos, Jovanny Zabaleta, Jiande Wu, Mary Anne Lynch, Luis Del Valle, Xiao-Cheng Wu, Augusto Ochoa, Chindo Hicks, Lucio Miele. Understanding triple-negative breast cancer immune microenvironment by disease stages, obesity, and race [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2525.