Volume of mammographic density and risk of breast cancer.

BACKGROUND Assessing the volume of mammographic density might more accurately reflect the amount of breast volume at risk of malignant transformation and provide a stronger indication of risk of breast cancer than methods based on qualitative scores or dense breast area. METHODS We prospectively collected mammograms for women undergoing screening mammography. We determined the diagnosis of subsequent invasive or ductal carcinoma in situ for 275 cases, selected 825 controls matched for age, ethnicity, and mammography system, and assessed three measures of breast density: percent dense area, fibroglandular volume, and percent fibroglandular volume. RESULTS After adjustment for familial breast cancer history, body mass index, history of breast biopsy, and age at first live birth, the ORs for breast cancer risk in the highest versus lowest measurement quintiles were 2.5 (95% CI: 1.5-4.3) for percent dense area, 2.9 (95% CI: 1.7-4.9) for fibroglandular volume, and 4.1 (95% CI: 2.3-7.2) for percent fibroglandular volume. Net reclassification indexes for density measures plus risk factors versus risk factors alone were 9.6% (P = 0.07) for percent dense area, 21.1% (P = 0.0001) for fibroglandular volume, and 14.8% (P = 0.004) for percent fibroglandular volume. Fibroglandular volume improved the categorical risk classification of 1 in 5 women for both women with and without breast cancer. CONCLUSION Volumetric measures of breast density are more accurate predictors of breast cancer risk than risk factors alone and than percent dense area. IMPACT Risk models including dense fibroglandular volume may more accurately predict breast cancer risk than current risk models.