Association of Breast Density with Breast Cancer Risk and Stage at Diagnosis: A Korean Nationwide Cohort Study.

BACKGROUND/OBJECTIVES: Breast density, as defined by the Breast Imaging Reporting and Data System (BI-RADS), reduces mammographic sensitivity and is a risk factor for breast cancer. However, its association with cancer risk and stage at diagnosis remains debated, with limited large-scale evidence. METHODS: We conducted a nationwide retrospective cohort study of 952,755 Korean women who underwent screening mammography between 2013 and 2014, with breast cancer diagnoses identified over a 5-year follow-up period. Breast density was categorized by BI-RADS criteria (A-D). Breast cancer risk was evaluated using logistic regression, with odds ratios representing relative odds of developing breast cancer during the 5-year interval. Stage at diagnosis was classified as localized versus regional/distant disease according to national cancer registry records. RESULTS: During 5 years of follow-up, 11,286 women (1.2%) were diagnosed with breast cancer. Higher breast density was significantly associated with increased breast cancer risk: multivariable-adjusted odds ratios (ORs) were 1.174 (95% CI, 1.093-1.260), 1.268 (95% CI, 1.186-1.356), and 1.287 (95% CI, 1.196-1.385) for BI-RADS B-D, respectively, compared with BI-RADS A (all p < 0.001). However, the risk of advanced stage (regional/distant vs. localized) disease at diagnosis did not significantly differ across breast density categories except for a modest association in BI-RADS B (OR 1.16, 95% CI, 1.01-1.33; p = 0.035). CONCLUSIONS: Higher breast density was independently associated with increased breast cancer risk but not with advanced-stage disease at diagnosis. These findings underscore the importance of individualized screening strategies for women with dense breasts.