Abstract 4173: Lipidome of mammographic breast density in premenopausal women

Abstract Introduction: High mammographic breast density (MBD) is a strong risk factor for breast cancer, but the biological mechanisms underlying high MBD are not well understood. We, therefore, comprehensively investigated for the first time the associations of lipid species with volumetric measures of MBD to elucidate potential biological mechanisms of high MBD in premenopausal women. Methods: We performed lipidomic profiling on 705 premenopausal women recruited during their annual screening mammogram at Washington University School of Medicine, St. Louis, MO. Lipidomic profiling for 982 lipid species was completed at Metabolon (Durham, NC®). Lipid species with greater than 300 missing values (N=125) were excluded from the analysis. Using nearest neighbor methods, we imputed the lipid species missing less than 300 values. We used Volpara 1.5 (Volpara Health®) to quantify volumetric measures of MBD - volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV). We investigated the associations of the lipid species with MBD measures using multivariable linear regression models adjusting for age, age at menarche, body shape at age 10, race/ethnicity, body fat %, family history of breast cancer, oral contraceptive use, parity/age at first birth, and alcohol use. MBD measures were log10-transformed, and lipid species were standardized. Linear coefficients were back-transformed to the original scale and considered significant if the Bonferroni corrected p<0.05. Results: In multivariable linear regression models, 34 lipid species were inversely associated with VPD. The lipid species belong to the triacylglycerol (TAG, N=26), diacylglycerol (DAG, N=6), phosphatidylcholine (PC, N=1), and cholesterol ester (N=1) pathways. DAG(16:0/18:2) and TAG54:6-FA20:4 displayed the largest inverse associations with one standard deviation increase in DAG(16:0/18:2), and TAG54:6-FA20:4 corresponding to 9.9% (p=0.002), and 9.6% (p=0.007) decrease in VPD, respectively. Eleven lipid species were significantly associated with NDV, with 10 species (all TAG) having a positive association and 1 inverse association PC(18:1/18:1). The strongest positive association was observed with TAG54:6-FA20:4. One standard deviation increase in TAG54:6-FA20:4 was associated with a 9.8% increase in NDV (p=0.01). Several of the lipid species (N=8, 23.5%) that were associated with VPD were also associated with NDV, but in opposite directions. No lipid species were significantly associated with DV. Conclusions: Our study identified many lipid species, especially in TAG and DAG pathways, that were associated with VPD and NDV and offer new insights into the biological mechanisms underlying high MBD in premenopausal women. Future studies are needed to validate our results and the translational potential. Citation Format: Kayla R. Getz, Myung S. Jeon, Chongliang Luo, Jingqin Luo, Adetunji T. Toriola. Lipidome of mammographic breast density in premenopausal women. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4173.