Dataset Information

Benign breast disease and changes in mammographic breast density.

ABSTRACT:

Background

Mammographic breast density (MBD) and benign breast disease (BBD) are two of the strongest risk factors for breast cancer. Understanding trends in MBD by age and parity in women with BBD is essential to the clinical management and prevention of breast cancer.

Methods

Using data from the Early Determinants of Mammographic Density (EDMD) study, a prospective follow-up study of women born in 1959-1967, we evaluated MBD in 676 women. We used linear regression with generalized estimating equations to examine associations between self-reported BBD and MBD (percent density, dense area, and non-dense area), assessed through a computer-assisted method.

Results

A prior BBD diagnosis (median age at diagnosis 32 years) was reported by 18% of our cohort. The median time from BBD diagnosis to first available study mammogram was 9.4 years (range 1.1-27.6 years). Women with BBD had a 3.44% higher percent MBD (standard error (SE) = 1.56, p-value = 0.03) on their first available mammogram than women without BBD. Compared with parous women without BBD, nulliparous women with BBD and women with a BBD diagnosis prior to first birth had 7-8% higher percent MBD (β = 7.25, SE = 2.43, p-value< 0.01 and β = 7.84, SE = 2.98, p-value = 0.01, respectively), while there was no difference in MBD in women with a BBD diagnosis after the first birth (β = -0.22, SE = 2.40, p-value = 0.93).

Conclusion

Women with self-reported BBD had higher mammographic breast density than women without BBD; the association was limited to women with BBD diagnosed before their first birth.

SUBMITTER: Reimers LL

PROVIDER: S-EPMC8074418 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.