Mammographic density: a heritable risk factor for breast cancer.

The appearance of the breast on mammography varies among women, reflecting variations in tissue composition. Stroma and epithelium attenuate x-rays more than fat and appear light on a mammogram, which we refer to here as " mammographic density, " while fat appears dark. We show evidence that mammographic density is a strong risk factor for breast cancer, and that risk of breast cancer is four to five times greater in women with density in more than 75% of the breast, compared with those with little or no density. Density in more than 50% of the breast may account for a large proportion of breast cancers. Density is influenced by age, parity, body mass index, and menopause but these factors account for only 20 - 30% of the variation in density in the population. Twin studies have shown that percent mammographic density, at a given age, is highly heritable, and that inherited factors explain 63% of the variance. Mammographic density has the characteristics of a quantitative trait, and may be influenced by genes that are easier to identify than those associated with breast cancer itself. The genes that influence mammographic density may also be associated with risk of breast cancer, and their identification is also likely to provide insights into the biology of the breast, and to identify potential targets for preventive strategies.