Screen-Film Mammographic Density and Breast Cancer Risk: A Comparison of the Volumetric Standard Mammogram Form and the Interactive Threshold Measurement Methods

Background: Mammographic density is a strong risk factor for breast cancer, usually measured by an area-based threshold method that dichotomizes the breast area on a mammogram into dense and nondense regions. Volumetric methods of breast density measurement, such as the fully automated standard mammogram form (SMF) method that estimates the volume of dense and total breast tissue, may provide a more accurate density measurement and improve risk prediction. Methods: In 2000-2003, a case-control study was conducted of 367 newly confirmed breast cancer cases and 661 age-matched breast cancer-free controls who underwent screen-film mammography at several centers in Toronto, Canada. Conditional logistic regression was used to estimate odds ratios of breast cancer associated with categories of mammographic density, measured with both the threshold and the SMF (version 2.2β) methods, adjusting for breast cancer risk factors. Results: Median percent density was higher in cases than in controls for the threshold method (31% versus 27%) but not for the SMF method. Higher correlations were observed between SMF and threshold measurements for breast volume/area (Spearman correlation coefficient = 0.95) than for percent density (0.68) or for absolute density (0.36). After adjustment for breast cancer risk factors, odds ratios of breast cancer in the highest compared with the lowest quintile of percent density were 2.19 (95% confidence interval, 1.28-3.72; Pt <0.01) for the threshold method and 1.27 (95% confidence interval, 0.79-2.04; Pt = 0.32) for the SMF method. Conclusion: Threshold percent density is a stronger predictor of breast cancer risk than the SMF version 2.2β method in digitized images. Cancer Epidemiol Biomarkers Prev; 19(2); 418–28