Associations of early-adulthood adiposity with breast parenchymal tissue complexity within premenopausal women

Background: Early-adulthood adiposity is associated with breast cancer risk. This study aims to evaluate the associations of early-adulthood adiposity with an emerging biomarker of breast cancer risk, breast parenchymal complexity, within premenopausal women. Methods: We retrospectively analyzed early-adulthood adiposity data and screening digital mammograms (DMs) of 326 premenopausal women (age in years; median: 48; range: 34–58) recruited at our institution. Adiposity measures were either assessed by trained personnel or self-reported by participants. DMs were analyzed using a well-validated computational imaging pipeline consisting of automated breast segmentation and radiomic feature extraction modules. The extracted radiomic features were fused into woman-specific breast parenchymal complexity feature vectors via principal component analysis, which were then used to identify distinct breast parenchymal complexity clusters via hierarchical clustering. Associations between each early-adulthood adiposity measure and breast parenchymal complexity clusters were assessed via logistic regression models and odds ratios (ORs) with the higher complexity cluster as reference. Associations between each early-adulthood adiposity measures with principal components were assessed via linear regression models and regression coefficients (b). All models were adjusted for age at screening, race, family history of breast cancer, and parity. Results: Two statistically significant clusters of high and low breast parenchymal complexity (p value < 0.001) were identified. Women with higher weight and body-mass index at ages 18 and 30 and larger weight increases over time were associated with lower breast parenchymal complexity, based on regression analysis of complexity clusters (1.04 ≤ OR ≤ 2.46) and principal components (0.13 ≤ b ≤ 6.76). Strongest associations were found for annual weight changes from age 18 to age at DM screening (mean change: 0.81 kg/year; OR = 2.46, 95% CI: [1.52, 3.98]; b = 6.76, 95% CI: [5.53, 8.00]) and from age 30 to age at DM screening (mean change: 0.78 kg/year; OR = 1.60, 95% CI: [1.20, 2.12]; b = 3.33, 95% CI: [2.56, 4.11]). Conclusion: Our preliminary data suggest that adiposity in early adulthood, as well as weight gain during early adulthood, may have a lifelong impact on breast parenchymal tissue patterns within premenopausal women. The inverse associations with breast parenchymal complexity may indicate a protective effect of of early-adulthood adiposity on breast cancer risk.