Abstract 4431: Steroid hormone metabolites and mammographic breast density in premenopausal women
Authors: Matthew Kayode A. , Vanapali Girish K. , Getz Kayla R. , Jeon Myung S. , Luo Chongliang , Guo Xingyi , Luo Jingqin , Toriola Adetunji T. 
Published: March 2024

Abstract
Background: Steroid hormones influence breast tissue development and play a role in breast carcinogenesis. Their associations with mammographic breast density (MBD), an established risk factor for breast cancer, are less clear. We, therefore, investigated the associations of steroid hormone metabolites with MBD in premenopausal women.
Methods: Our study population consists of 705 premenopausal women recruited during their annual screening mammogram at the Washington University School of Medicine, St. Louis, MO. We assessed volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV) using Volpara. We assayed 54 steroid hormone metabolites from fasting blood samples at Metabolon. Linear regression models were used, after adjusting for covariates, to estimate the least square means of VPD, DV, and NDV across tertiles (T) of each metabolite. Sensitivity analysis was performed among the subset of participants with a history of oral contraceptive use (OCP). We used the Benjamini-Hochberg procedure to correct for multiple tests to control the false discovery rate (FDR) at a 5% level.
Results: Five androgen metabolites (androstenediol (3beta,17beta) monosulfate 2, androstenediol (3beta,17beta) disulfate 1, 5alpha-androstan-3alpha,17beta-diol monosulfate 2, 5alpha-androstan-3alpha,17beta-diol disulfate, and 5alpha-androstan-3beta,17beta-diol disulfate) and two corticosteroid metabolites (tetrahydrocortisone glucuronide 5, and cortolone glucuronide 1) were inversely associated with VPD. Androstenediol (3beta,17beta) disulfate 1, and 5alpha-androstan-3alpha,17beta-diol disulfate displayed the strongest associations with VPD. The mean VPD decreased across tertiles of androstenediol (3beta,17beta) disulfate 1 from 9.0% in T1 to 8.5% in T2, and 7.5% in T3 (FDR p-value=0.02). Similarly, the mean VPD decreased from 8.8% in T1 to 8.4% in T2, and 7.6% in T3 of 5alpha-androstan-3alpha,17beta-diol disulfate (FDR p-value=0.03). Progestin steroid metabolites appeared to be positively associated with VPD but only 5alpha-pregnan-3beta,20alpha-diol monosulfate 2 was marginally significant after FDR correction (7.5% in T1, 8.3% in T2, and 8.8% in T3; FDR p-value=0.06). Four metabolites (three corticosteroids and one androgenic steroid) were positively associated with NDV. No metabolite was associated with DV. In sensitivity analysis limited to OCP users, mean VPDs were lower but the directions of associations were similar to those observed in the overall analysis.
Conclusion: We report novel associations of corticosteroids and androgen metabolites with breast density in premenopausal women. Our findings shed important new insights into hormonal biomarkers and MBD.
Citation Format: Kayode A. Matthew, Girish K. Vanapali, Kayla R. Getz, Myung S. Jeon, Chongliang Luo, Xingyi Guo, Jingqin Luo, Adetunji T. Toriola. Steroid hormone metabolites and mammographic breast density in premenopausal women [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4431.