Variation in risk and outcomes of Epstein–Barr virus-associated breast cancer by epidemiologic characteristics and virus detection strategies: an exploratory study

Purpose: A relationship of Epstein–Barr virus (EBV) and breast cancer etiology and outcome may have clinical utility and potential to enhance understanding of tumor biology. Research to date has yielded variable results, likely reflecting differing virus detection assays and unaddressed epidemiologic heterogeneity across studies. Methods: Applying our novel, five-target assay detection strategy in an exploratory study, we examined demographic, clinical, and tumor characteristics, and overall survival, associated with EBV positivity in breast adenocarcinomas from 59 non-Hispanic white and 68 Hispanic women sampled by age (<50, 50+) and stage (localized, regional/remote) and examined associations based on single assay targets. Results: EBV was localized only to lymphocytes. Nevertheless, viral prevalence, although low, varied across patient subgroups. Adjusted odds ratios (OR) for EBV positivity were lower for younger Hispanic than white women (p_interaction = 0.05), and marginally higher for larger [OR (95% confidence intervals) 1.03 (1.00–1.05) per mm increase] and right-sided [2.8 (0.97–7.8)] tumors. In whites, ORs were marginally higher for larger tumors [1.04 (1.00–1.07)] and marginally lower for age 50+ [0.24 (0.06–1.03)]; in Hispanics, ORs were higher for ER negative [5.6 (1.1–30.5)], and marginally higher for right-sided, tumors [5.8 (0.94–36.2)]. Survival was suggestively poorer for EBV-positive than EBV-negative tumors in older women with localized disease. EBV associations differed across single assay targets, indicating variation in prior findings likely due to assay performance. Conclusions: The differing EBV associations by age and race/ethnicity suggest a non-random role of EBV in breast cancer and support further study using multi-target assays, relevant epidemiologic design, and a larger study sample.