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. 2023 Oct 9;25(1):121.
doi: 10.1186/s13058-023-01725-1.

Lipidome of mammographic breast density in premenopausal women

Kayla R Getz  1 , Myung Sik Jeon  1   2 , Chongliang Luo  1   2 , Jingqin Luo  1   2 , Adetunji T Toriola  3   4
Affiliations

Lipidome of mammographic breast density in premenopausal women

Kayla R Getz et al. Breast Cancer Res. .

Abstract

Background: High mammographic breast density (MBD) is a strong risk factor for breast cancer development, but the biological mechanisms underlying MBD are unclear. Lipids play important roles in cell differentiation, and perturbations in lipid metabolism are implicated in cancer development. Nevertheless, no study has applied untargeted lipidomics to profile the lipidome of MBD. Through this study, our goal is to characterize the lipidome of MBD in premenopausal women.

Methods: Premenopausal women were recruited during their annual screening mammogram at the Washington University School of Medicine in St. Louis, MO. Untargeted lipidomic profiling for 982 lipid species was performed at Metabolon (Durham, NC®), and volumetric measures of MBD (volumetric percent density (VPD), dense volume (DV), and non-dense volume (NDV)) was assessed using Volpara 1.5 (Volpara Health®). We performed multivariable linear regression models to investigate the associations of lipid species with MBD and calculated the covariate-adjusted least square mean of MBD by quartiles of lipid species. MBD measures were log10 transformed, and lipid species were standardized. Linear coefficients of MBD were back-transformed and considered significant if the Bonferroni corrected p-value was < 0.05.

Results: Of the 705 premenopausal women, 72% were non-Hispanic white, and 23% were non-Hispanic black. Mean age, and BMI were 46 years and 30 kg/m2, respectively. Fifty-six lipid species were significantly associated with VPD (52 inversely and 4 positively). The lipid species with positive associations were phosphatidylcholine (PC)(18:1/18:1), lysophosphatidylcholine (LPC)(18:1), lactosylceramide (LCER)(14:0), and phosphatidylinositol (PI)(18:1/18:1). VPD increased across quartiles of PI(18:1/18:1): (Q1 = 7.5%, Q2 = 7.7%, Q3 = 8.4%, Q4 = 9.4%, Bonferroni p-trend = 0.02). The lipid species that were inversely associated with VPD were mostly from the triacylglycerol (N = 43) and diacylglycerol (N = 7) sub-pathways. Lipid species explained some of the variation in VPD. The inclusion of lipid species increased the adjusted R2 from 0.45, for a model that includes known determinants of VPD, to 0.59.

Conclusions: We report novel lipid species that are associated with MBD in premenopausal women. Studies are needed to validate our results and the translational potential.

Keywords: Lipidomics; Mammographic breast density; Premenopausal.

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Conflict of interest statement

The authors have no relevant financial or non-financial interests to disclose.

Figures

Fig. 1
Fig. 1
Covariate-adjusted Associations between Lipid Sub-pathways with VPD and NDV A volcano plot of lipid sub pathways for VPD, B volcano plot lipid sub-pathways for NDV, C Venn diagram of lipid sub-pathways for VPD, DV and NDV Abbreviations: volumetric percent density (VPD), non-dense volume (NDV) dihydroceramide (DCER), lactosylceramide (LCER), diacylglycerol (DAG), triacylglycerol (TAG)
Fig. 2
Fig. 2
Covariate-adjusted Associations between Lipid Species with VPD and NDV A volcano plot of lipid species for VPD, B volcano plot of lipid species for NDV, C Venn diagram of lipid species for VPD, DV and NDV. Abbreviations: volumetric percent density (VPD), non-dense volume (NDV) lysophosphatidylcholine (LPC), phosphatidylinositol (PI), lactosylceramide (LCER), diacylglycerol (DAG), phosphatidylcholine (PC), triacylglycerol (TAG)
See this image and copyright information in PMC

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