Abstract 2372: Circulating pre-diagnosis immune markers and breast cancer risk: findings from the Cancer Prevention Study-3

Abstract Background: Breast cancer is recognized as potentially immunogenic with early evidence suggesting patients may benefit from immunotherapy. Cytokines including tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), and those from the interleukin (IL) family (IL-6, IL-8, and IL-10) play a critical role in immune system regulation. However, the association of pre-diagnostic cytokines levels with breast cancer risk remains unclear with few studies reporting inconsistent findings. Objective: The goal of this study was to examine associations between circulating cytokines (IL-6, IL-8, and IL-10, TNF-α and IFN-γ) and subsequent breast cancer risk. Methods: For this study, we utilized data from the Cancer Prevention Study 3 (CPS-3), a prospective cohort study initiated by the American Cancer Society (ACS), which fully enrolled 198, 632 women aged 30-65 years from 2006-2013, across 35 states, Washington D.C., and Puerto Rico. A nested case-control design was used for this study. The analytic sample included 606 primary invasive breast cancer cases, matched to 606 controls based on age at study enrollment, race, blood draw date, and menopausal status. Blood collected at CPS-3 enrollment was used to quantify five immune markers of inflammation and immune regulation: IL-6, IL-8, IL-10, IFN-γ, and TNF-α using the V-PLEX multiplex immunoassay at the International Agency for Research on Cancer (IARC). Each immune marker was analyzed both as a continuous and a categorical (quartiles) variable. Conditional logistic regression was used to estimate odds ratios for the association between each immune marker and overall breast cancer risk. Results: The median age at diagnosis was 54 years (interquartile range (IQR): 48, 59). Cases and controls were fairly comparable across key demographic, clinical and behavioral variables. For every one-unit increase in log-transformed IFN-γ, the odds of breast cancer decreased by 16% (OR=0.84, 95% CI: 0.72-0.99). All other immune markers were not significantly associated with overall breast cancer risk. Conclusion: With the exception of IFN-γ, the findings do not provide evidence that these selected immune markers are associated with breast cancer risk. Given the heterogenous nature of breast cancer, future studies should consider breast cancer molecular and histologic subtypes and potential modifications by other clinical and tumor characteristics. Citation Format: Shamim Shahi, James Hodge, Mia Gaudet, Alpa V. Patel, Laure Dossus, Sabina Rinaldi, Lauren Teras. Circulating pre-diagnosis immune markers and breast cancer risk: findings from the Cancer Prevention Study-3 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2372.