Abstract PS3-02-25: A blood-based lipid panel for risk determination of harboring breast cancer among women at elevated risk

Abstract There remains a need to establish tools to better tailor screening for women at elevated risk of breast cancer (BrCa). Alterations in metabolism are inherently intertwined with breast cancer development and progression. In the current study, we performed multi-assay metabolomic analyses on plasma samples collected from a total of 438 breast cancer cases and 311 female controls from two independent cohorts of high-risk women. Samples from one cohort were used for discovery and samples from the second cohort were used for initial pre-validation. Machine learning was applied to establish a 12-lipid marker panel and tertile-based thresholds for low-, intermediate-, and high-risk of harboring breast cancer subsequently established. The lipid panel and corresponding risk thresholds were further validated in an independent nested case-control cohort of women at elevated risk, using plasma samples prospectively collected from 81 women who developed invasive breast cancer and 191 age-matched female controls. The lipid panel achieved ORs [per unit increase] of 2.31, 2.37, 1.48, in the respective Discovery, Pre-Validation, and Validation Sets. In the combined datasets, the lipid panel yielded an overall OR of 2.02 and AUC of 0.67 for BrCa. Compared to women in the low-risk strata, women in the high-risk group based on the lipid panel were 3.48-times more likely to have BrCa. The lipid panel provides a potential tool for stratifying women at highest risk of developing or harboring breast cancer who would benefit from more intensive screening and interception strategies from those at lowest risk who may be spared overdiagnosis and overtreatment. Citation Format: E. Irajizad, S. Hanash, J. Fahrmann, A. Brewster. A blood-based lipid panel for risk determination of harboring breast cancer among women at elevated risk [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-25.