Abstract P4-10-01: Evaluation of the role of EBV in breast cancer

Abstract

Abstract Background: A number of factors, both modifiable and non-modifiable, are associated with increased risk of developing breast cancer. Although these factors may help predict risk and prognosis, these known factors are imperfect and suggest that additional factors exist that promote the development and behavior of breast cancer. The Epstein-Barr virus (EBV), which is associated with tumor types such as Burkitt’s lymphoma and gastric cancer, may contribute to breast cancer development and/or progression, however, current research has led to mixed results, with some groups finding a positive correlation between EBV and breast cancer and others failing to find an association. Methods: The Clinical Breast Care Project database was queried to identify patients with high-quality, research-grade frozen tumor specimens and serum samples available. Previous exposure to EBV was determined using the Epstein-Barr virus (EBNA) IgG Human ELISA Kit. EBV, B-cells and macrophages were detected by immunofluorescence (IF) in seropositive patients using probes for EBNA1, CD-68 and CD-20, respectively. EBV and B-cell status was scored as present or absent while macrophages were classified as sparse, focal (weak, moderate or strong expression) or disseminated (macrophages detected throughout the tumor and stroma). Results: ELISA analysis on 211 serum samples found that 202 (96%) patients were seropositive for past EBV exposure. IF data has been generated for 31 tumors, from which six had no detectable B-cells. Of the remaining B-cell positive tumors, 32% (8/25) were positive for EBNA1 within the B-cells. Distribution of intrinsic subtypes was similar between both EBV+ and EBV- tumors, however, diagnosis with a late-stage tumor and lymph node metastasis was higher in EBV+ (50% stage III/IV, 88% lymph node positive) compared to EBV- tumors (24% stage III/IV, 47% lymph node positive). In addition, EBV+ tumors were more likely to have sparse/focal(weak) macrophage staining (63%) compared to EBV- tumors (47%). Conclusions: These data demonstrate that latent EBV is present within B-cells in a significant number of invasive breast tumors. Decreased detection of macrophages within the tumor component supports the theory that expression of EBV proteins impairs the function and maturation of macrophages, thus impairing immune surveillance and creating a pro-tumorigenic environment. This altered immune response may contribute to the later stage and increased frequency of metastasis in patients with EBV positive B-cells within the tumor microenvironment. Citation Format: Rachel E Ellsworth, Jill D Henning, Nikki Oakes, Allyson L Valente, Brednda Deyarmin, Jeff Meyer, Matthew T Hueman, Craig D Shriver. Evaluation of the role of EBV in breast cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-10-01.