Mammographic Density and Breast Cancer Risk: Evaluation of a Novel Method of Measuring Breast Tissue Volumes

Background: Mammographic density has been found to be strongly associated with risk of breast cancer. We have assessed a novel method of assessing breast tissue that is fully automated, does not require an observer, and measures the volume, rather than the projected area, of the relevant tissues in digitized screen-film mammogram. Methods: Sixteen mammography machines in seven locations in Toronto were calibrated to allow the estimation of the proportion of radiologically dense (stromal and epithelial tissue) and nondense (fatty) tissue represented in each pixel of the mammographic image. This information was combined with a measurement of breast thickness to calculate the volumes of these tissues. Women with newly diagnosed breast cancer (cases) identified on these mammography machines during the years 2000 to 2003 were compared with other women of the same age who did not have breast cancer (controls). Results: Three hundred sixty-four cases and 656 controls were recruited, epidemiologic data were collected, screen-film mammograms were digitized and measured using both a computer-assisted thresholding method, and the new measure of the volume of density. After adjustment for other risk factors, the odds ratio for those in the 5th quintile compared with the 1st quintile was 1.98 (95% confidence interval, 1.3-3.1) for the volume measure and 1.86 (95% CI, 1.1-3.0) for the area measurement. After inclusion of the volume and area measures in a predictive model, the volume measure lost significance, whereas the area measure remained significant. Conclusions: Contrary to our expectations, measurement of the volume of breast tissue did not improve prediction of breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1754–62)