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Hormonal determinants of mammographic density and density change.

ABSTRACT: BACKGROUND:Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm2) and annual MD change (cm2/year). METHODS:This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n?=?3), androgen (n?=?7), oestrogen (n?=?2) and corticoid (n?=?5) pathways were analysed by ultra-performance supercritical fluid chromatography-tandem mass spectrometry (UPSFC-MS/MS), as well as peptide hormones and proteins (n?=?2). MD was measured as a dense area using the STRATUS method (mean over the left and right breasts) and mean annual MD change over time. RESULTS:Greater baseline mean MD was associated with overall higher concentrations of progesterone (average +?1.29?cm2 per doubling of hormone concentration), 17OH-progesterone (+?1.09?cm2), oesterone sulphate (+?1.42?cm2), prolactin (+?2.11?cm2) and SHBG (+?4.18?cm2), and inversely associated with 11-deoxycortisol (-?1.33?cm2). The association between MD and progesterone was confined to the premenopausal women only. The overall annual MD change was -?0.8?cm2. Hormones from the androgen pathway were statistically significantly associated with MD change. The annual MD change was -?0.96?cm2 and -?1.16?cm2 lesser, for women in the highest quartile concentrations of testosterone and free testosterone, respectively, compared to those with the lowest concentrations. CONCLUSIONS:Our results suggest that, whereas hormones from the progestogen, oestrogen and corticoid pathways drive baseline MD, MD change over time is mainly driven by androgens. This study emphasises the complexity of risk factors for breast cancer and their mechanisms of action.

SUBMITTER: Gabrielson M

PROVIDER: S-EPMC7449090 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Hormonal determinants of mammographic density and density change.

Gabrielson Marike M Azam Shadi S Hardell Elina E Holm Madeleine M Ubhayasekera Kumari A KA Eriksson Mikael M Bäcklund Magnus M Bergquist Jonas J Czene Kamila K Hall Per P

Breast cancer research : BCR 20200826 1

<h4>Background</h4>Mammographic density (MD) is a strong risk factor for breast cancer. We examined how endogenous plasma hormones are associated with average MD area (cm<sup>2</sup>) and annual MD change (cm<sup>2</sup>/year).<h4>Methods</h4>This study within the prospective KARMA cohort included analyses of plasma hormones of 1040 women. Hormones from the progestogen (n = 3), androgen (n = 7), oestrogen (n = 2) and corticoid (n = 5) pathways were analysed by ultra-performance supercritical flu ...[more]

PMID: 32847607

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Project description:BackgroundBecause of the mixed reports from smaller studies, we examined associations of race with mammographic breast density and evaluated racial differences in the determinants of breast density.MethodsParticipants included 37 839 women (23 166 non-Hispanic white and 14 673 African American) receiving screening mammograms at the Joanne Knight Breast Health Center at Washington University School of Medicine from June 2010 to December 2015. Mammographic breast density was assessed using the Breast Imaging Reporting and Data System (5th edition). To determine the association of race and participant characteristics with mammographic breast density, we used multivariable polytomous logistic regression models (reference group: almost entirely fatty).ResultsAfrican American women had increased odds of extremely dense (adjusted odds ratio = 1.31, 95% confidence interval = 1.13 to 1.52) and reduced odds of heterogeneously dense breasts (adjusted odds ratio = 0.91, 95% confidence interval = 0.84 to 0.99) compared with non-Hispanic white women. Altogether, race, parity and age at first birth, current age, current body mass index (BMI), BMI at age 18 years, menarche, family history of breast cancer, oral contraceptive use, alcohol use, and menopausal status explained 33% of the variation in mammographic breast density. Among African American and non-Hispanic white women, these factors explained nearly 28.6% and 33.6% of the variation in mammographic density, respectively. Current BMI provided the greatest explanation of breast density (26.2% overall, 22.2% in African American, and 26.2% in non-Hispanic white women).ConclusionsThe determinants of mammographic breast density were generally similar between African American women and non-Hispanic white women. After adjustments for confounders, African Americans had higher likelihood of extremely dense breasts but lower likelihood of heterogeneously dense breasts. The greatest explanation of breast density was provided by BMI, regardless of race.

Project description:Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and generalized regression models were used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest among young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer.

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Hormonal determinants of mammographic density and density change.

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Hormonal determinants of mammographic density and density change.

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