Abstract

Abstract Background: Women of African ancestry (AA) have higher breast cancer mortality than other US racial/ethnic groups, attributed to a number of social and economic factors. However, breast tumors in AA women are more likely to present with higher grade and lacking estrogen receptor (ER) expression compared to those from women of European ancestry (EA), suggesting the importance of tumor factors in breast cancer disparities. Emerging evidence suggests that stromal tumor-infiltrating lymphocytes (TIL-str) have a role in immune response to therapy and prognosis of breast cancer. The objective of this study was to examine associations between risk factors for breast cancer and TIL-str, with consideration of tumor characteristics. Methods: We reviewed the hematoxylin and eosin slides from surgical or biopsy tumor blocks of invasive breast cancer from 1,385 cases (986 AA and 399 EA women, aged 20-75 years) in the Women's Circle of Health Study, a multicenter case-control study in New York and New Jersey. In-person interviews were conducted at diagnosis to obtain data on demographics, family histories, hormone use, and reproductive and menstrual histories. Anthropometric measurements were taken by trained staff. TIL-str were scored as 0%, 1%, and 10% to 100% in increments of 10%. Linear regressions were performed to estimate differences in TIL-str scores (β). Results: In univariate analysis, TIL-str was higher in tumors from AA than those from EA women overall (mean score = 21.5% vs. 12.5; P<0.001). TIL-str score was positively associated with higher grade, larger tumor size, and ER and progesterone receptor (PR) negativity in both AA and EA women (all P<0.05). In EA women, TIL-str score was also higher in more advanced than early stage tumors and human epidermal factor receptor 2 (HER2) positive than negative tumors (both P<0.05), but not in AA women. In multivariable analysis, AA compared to EA race was significantly associated with a higher TIL-str score (β = 5.7%, P<0.001), adjusting for age at diagnosis, body mass index, menopausal status, tumor grade, size, stage, and molecular subtypes defined by ER, PR, and HER2. There was no apparent association between TIL-str and history of breast cancer in first-degree relatives, history of benign breast disease, hormone use, reproductive factors, or body size. Conclusion: Self-reported African compared to European ancestry is independently associated with higher TIL-str scores in breast tumors. Our findings suggest that immune response may play a role in the differences in breast cancer biology and outcomes between AA and EA women. (Funding: The Breast Cancer Research Foundation; NIH P01CA151135, R01CA100598, R01CA185623, P30CA072720, K07CA201334; US Army Medical Research and Material Command DAMD-17-01-1-0334) Citation Format: Ting-Yuan D. Cheng, Rochelle Payne Ondracek, Song Yao, Warren Davis, Angela Omilian, Mateusz Opyrchal, Elisa V. Bandera, Michael J. Higgins, Christine B. Ambrosone, Thaer Khoury. Differences in stromal tumor-infiltrating lymphocytes in breast cancer from women of African and European ancestry after accounting for tumor characteristics [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 3242.

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