Breast density and risk of breast cancer: masking and detection bias.

Breast density is associated with risk of breast cancer (BC) diagnosis, affecting risk prediction tools and patient notification policies. Density affects mammography sensitivity and may influence screening intensity. Therefore, the observed association between density and BC diagnosis may not reflect the relationship between density and disease risk. We investigated the association between breast density and BC risk using data sourced from 33 542 women in the Breast Cancer Surveillance Consortium, 2000-2018. We estimated mammogram sensitivity and rates of screening mammography among dense (Breast Imaging Reporting and Data System [BI-RADS] breast density categories C and D) and nondense (BI-RADS categories A and B) breasts. We used Kaplan-Meier estimates to summarize the relative risks of BC diagnosis (RRdx) by density and fit a natural history model to estimate the relative risks of BC onset (RRonset) given density-specific sensitivities. The RRdx for dense vs nondense breasts was 1.80 (95% CI, 1.46-2.57). Based on estimated screening sensitivities of 0.88 and 0.78 for nondense and dense breasts, respectively, RRonset was 1.73 (95% CI, 1.43-2.25). Sensitivity analyses suggested higher breast density is robustly associated with increased risk of BC onset, similar in magnitude to the increased risk of BC diagnosis. These findings support laws requiring notifications to women with dense breasts of their increased BC risk.