Some previous studies, using qualitative methods of classifying mammographic features, have shown that women with a family history of the disease have more extensive mammographic density than women with no family history ( 16- 20), but other studies have failed to find this association ( 11, 21- 25). As PMD is a risk factor for breast cancer, and is highly heritable, it might account for some of the association of family history with risk of breast cancer. Twin studies have shown that >60% of the residual variance after adjustment for age and other covariates can be explained by inherited factors ( 5). These factors account for only about 20% to 30% of the variance of PMD. Body weight and age, however, are inversely associated with PMD ( 14, 15). PMD is lower in women who are parous or postmenopausal ( 10, 11), is increased by the use of hormone therapy ( 12), and is reduced by the use of tamoxifen ( 13). Percent mammographic density (PMD) is associated with several factors that are also associated with risk of breast cancer. Cancer Epidemiol Biomarkers Prev 19(2) 456–63 Percent mammographic density explained 14% (95% CI, 4-39%) of the association of family history (at least one affected first-degree relative) with breast cancer risk.Ĭonclusions: Percent mammographic density has features of an intermediate marker for breast cancer, and some of the genes that explain variation in percent mammographic density might be associated with familial risk of breast cancer. Adjustment for percent mammographic density reduced these odds ratios by 16% and 14%, respectively. The odds ratios for breast cancer risk were 1.37 for having one affected relative, and 2.45 (95% CI, 1.30-4.62) for having two or more affected relatives ( P for trend = 0.0002). Results: After adjustment for age and other risk factors, compared with women with no affected first-degree relatives, percent mammographic density was 3.1% greater for women with one affected first-degree relative, and 7.0% greater for women with two or more affected relatives ( P = 0.001 for linear trend across family history categories). We estimated the independent and combined associations of family history and percent mammographic density at baseline with subsequent breast cancer risk. Subjects and Methods: We carried out three nested case-control studies in screening programs that included in total 2,322 subjects (1,164 cases and 1,158 controls). The purpose of this study was to examine the extent to which mammographic density explains the association of family history of breast cancer with risk of the disease. Purpose: Mammographic density is a strong and highly heritable risk factor for breast cancer.
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