Mammographic breast density as a general marker of breast cancer risk.

A11

Mammographic density is a strong risk factor for breast cancer but whether breast density is a general marker of susceptibility or is specific to the location of the eventual cancer is not known. A clinic-based study of 372 incident breast cancer cases and 715 matched controls was conducted within the Mayo Clinic mammography screening practice. Breast cancer cases were women 50 years or older with primary invasive cancer (n=300) or ductal carcinoma in situ (n=72) diagnosed between 1997 and 2001 who had at least two prior screening mammograms two years prior to diagnosis. Controls from the screening practice were matched to each case on age (within 5 years), final screening exam date (4 months), menopausal status (pre or post), interval between mammograms (8 months), number of prior screening mammograms (1 mammogram) and residence (county). Mammograms on average 7 years prior to breast cancer (or corresponding exam date for controls) were digitized and quantitative measures of percent density and dense area from each side and view were estimated using a thresholding technique (Cumulus). A regional density estimate accounting for overall percent density was calculated from both mammogram views. Weight, height, hormone replacement therapy (HRT) and other potential confounders were abstracted from the medical record for the dates closest to the mammogram dates. Location of the breast tumor was abstracted from radiology or pathology reports. Conditional logistic regression was used to evaluate the associations of mammographic density and regional density with breast cancer risk. C-statistics were used to evaluate risk prediction. There were increasing trends in breast cancer risk with increasing quartiles of percent density and dense area, irrespective of the side of the breast with cancer (P-trend's < 0.001). Percent density from the ipsilateral side (CC: ORs=1.0 (ref), 1.7, 3.1, 3.1; MLO: ORs=1.0 (ref), 1.5, 2.2, 2.8) and the contralateral side (CC: ORs=1.0 (ref), 1.8, 2.2, 3.7; MLO: ORs=1.0 (ref), 1.6, 1.9, 2.5) similarly predicted case-control status (C-statistics=0.64-65). Accounting for overall percent density, density in the region where the cancer subsequently developed was not a significant risk factor (CC: 1.0 (ref), 1.3, 1.0, 1.2; MLO: 1.0 (ref), 1.1, 1.0, 1.1 for increasing quartiles). In terms of risk prediction, no additional benefit was evident when including the regional density measure (C-statistics 0.64-0.65). Examining mammograms closer to the cancer (on average 3 years) resulted in similar findings for cancer-region density and breast cancer risk. Overall mammographic density appears to represent a general marker of breast cancer risk in either breast. The association does not appear stronger in the region where the breast cancer eventually occurs.