The association of breast mitogens with mammographic densities

Differences between individuals of the same age in the radiological appearance of the breast reflect differences in tissue composition. Epithelial and stromal tissues attenuate X-rays more than does fat, and appear light on a mammogram, while fat appears dark (Johns and Yaffe, 1987). Extensive areas of light appearing tissue on a mammogram, referred to as ‘mammographic density’, have been found to be associated with 4–6-fold differences in the risk of breast cancer, after taking into account other known risk factors for the disease (Boyd et al, 1998). The biological basis for inter-individual variations in breast tissue composition, and for the association of these variations with risk of breast cancer is, however, unknown, although several factors are known to influence the radiographic appearance of the breast. Mammographic density decreases with greater parity, greater body weight, greater age (Boyd et al, 1998), and is increased by hormone replacement therapy (Lundstrom et al, 1999), and decreased by Tamoxifen (Atkinson et al, 1999; Brisson et al, 2000). All of these observations suggest that variations in exposure to endogenous hormones or growth factors may be responsible for the differences in breast tissue composition that are reflected in differences in the extent of mammographic density. The purpose of the present study was to examine, in a cross-sectional study design, the association between mammographic density and blood levels of endogenous hormones and growth factors. The hormones examined include total and free oestradiol and progesterone, sex hormone binding globulin (SHBG), growth hormone, insulin like growth factor-I (IGF-I), its principal binding protein - insulin-like growth factor binding protein-3 (IGFBP-3), and prolactin.