Beyond Mammographic Density: A Computational Imaging Approach to Identify Effects of Early Adulthood Adiposity on Breast Parenchymal Tissue Patterns in Premenopausal Women

Early-adulthood adiposity measures, such as weight and body-mass index, are associated with breast cancer risk. Moreover, studies have shown that breast parenchymal tissue patterns as reflected in digital mammograms (DMs) are also associated with breast cancer risk. We retrospectively analyzed DMs and early-adulthood adiposity data of 326 premenopausal women with the aim to assess the relationship of early-adulthood adiposity and breast parenchymal tissue patterns later in life. Radiomic features were extracted from DMs using a well-validated computational imaging pipeline and fused into woman-specific radiomic feature vectors via principal component analysis. Hierarchical clustering was then applied to radiomic feature vectors to identify distinct phenotypes (clusters) of breast parenchymal complexity. For each early-adulthood adiposity measure, its associations with the identified breast parenchymal complexity clusters were assessed via logistic regression, adjusted for age at screening, race, family history of breast cancer, and parity. Two statistically significant clusters of breast parenchymal complexity (p-value < 0.001), “cluster 0” and “cluster 1”, were identified on the basis of principal components. Compared to women of high breast parenchymal complexity (“cluster 0”), women assigned to the cluster of lower breast parenchymal complexity (“cluster 1”) were associated with higher early-adulthood adiposity and larger adiposity changes over time. Among all early-adulthood adiposity measures, strongest associations with breast parenchymal complexity clusters were found for annual weight change from age 18 to age at DM screening (odds ratio [OR] = 2.46, 95% CI: [1.52, 3.99]) and annual weight change from age 30 to age at DM screening (OR = 1.73, 95% CI: [1.25, 2.39]). Our preliminary data suggest that adiposity in early adulthood, as well as weight gain from early adulthood to attained age are inversely associated with breast parenchymal complexity among premenopausal women and may have a lifelong impact on breast parenchymal tissue patterns.