Abstract P2-10-02: Racial differences in infiltration of CD8+ T-cells in breast tumors of Black and White women
Authors: Abdou Yara , Yao Song , Attwood Kristopher , Zirpoli Gary , Bshara Wiam , Ambrosone Christine , Omilian Angela 
Published: March 2020

Background: Racial disparities in breast cancer outcome continues to be a major health care challenge. The reasons underlying this disparity are multifactorial with a recent focus on the tumor microenvironment. The characterization of infiltrating immune cell populations in the tumor microenvironment are lacking in Black breast cancer patients. To address this research gap, we employed immunohistochemical (IHC) staining and quantitative digital imaging to assess CD8+ T-cells in breast tumor samples from the Women’s Circle of Health Study (WCHS), a population-based case-control study of breast cancer in Black and White women. Our aim was to characterize and compare the density, localization and distribution of CD8+ T cells, and explore their prognostic value in each racial group.

Methods: Tumor-infiltrating CD8+ lymphocytes were assessed by IHC staining of tissue microarray (TMA) cores from 736 breast cancer patients, including 597 Blacks and 139 Whites. The Aperio platform was used for quantitative image analysis of TMA cores. Racial differences in demographic and clinical characteristics were evaluated using the Mann-Whitney U and Fisher’s exact tests. Overall (OS) and breast cancer-specific (DSS) survival were summarized by race using the Kaplan-Meier method and compared using the log-rank test. The associations between demographic/clinical factors and CD8 expression were evaluated using a general linear model (GLM). Multivariable Cox regression models were used to evaluate associations between survival outcomes and both race and CD8 expression, while adjusting for age.

Results: Black women had a higher percentage of high-grade tumors in addition to higher prevalence of ER-negative and triple negative tumors than white women. There was a statistically significant difference in OS (p=0.043), showing worse outcomes among Black patients. Black patients had significantly higher CD8+ expression compared to White patients, with mean values of 756.2/mm2 and 292.4/mm2 respectively (p&lt;0.001). This was consistent across all subtypes, with the highest CD8+ expression seen in Black patients with triple negative breast cancer (p&lt;0.001). Higher CD8+ expression was significantly correlated with higher tumor grade and higher Ki67 scores (p&lt;0.001). There was significantly higher expression of CD8+ T-cells in Stage II disease in comparison to stages I, III and IV in both races (p =0.01). Furthermore, there was a significant inverse relationship between age and CD8+ expression (p=0.002). Neoadjuvant chemotherapy did not seem to have a significant effect on CD8+ T-Cell expression (p=0.46). No significant associations were observed between CD8 expression in tertiles and OS or DSS overall or within each cancer subtype. Further analyses are being conducted to assess CD8+ T cells in the stromal and tumor segments.

Conclusions: We observed a stronger presence of CD8+ T cells in tumor microenvironment from Black breast patients, suggesting the existence of distinct tumor immune responses in this population. Our current data do not support that CD8+ T cells contribute to breast cancer survival disparities given the lack of prognostic significance of CD8 expression in this sample. CD8+ T cells may become less cytotoxic towards tumor cells as a result of immunosuppression or exhaustion; therefore, in-depth immuno-profiling of the versatile immune cell subsets and their qualities of breast tumor microenvironment in Black patients is warranted to understand their roles in breast cancer racial disparities.

Citation Format: Yara Abdou, Song Yao, Kristopher Attwood, Gary Zirpoli, Wiam Bshara, Christine Ambrosone, Angela Omilian. Racial differences in infiltration of CD8+ T-cells in breast tumors of Black and White women [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-10-02.