Breast Tissue Composition and Susceptibility to Breast Cancer

Abstract

Breast density, as assessed by mammography, reflects breast tissue composition. Breast epithelium and stroma attenuate x-rays more than fat and thus appear light on mammograms while fat appears dark. In this review, we provide an overview of selected areas of current knowledge about the relationship between breast density and susceptibility to breast cancer. We review the evidence that breast density is a risk factor for breast cancer, the histological and other risk factors that are associated with variations in breast density, and the biological plausibility of the associations with risk of breast cancer. We also discuss the potential for improved risk prediction that might be achieved by using alternative breast imaging methods, such as magnetic resonance or ultrasound. After adjustment for other risk factors, breast density is consistently associated with breast cancer risk, more strongly than most other risk factors for this disease, and extensive breast density may account for a substantial fraction of breast cancer. Breast density is associated with risk of all of the proliferative lesions that are thought to be precursors of breast cancer. Studies of twins have shown that breast density is a highly heritable quantitative trait. Associations between breast density and variations in breast histology, risk of proliferative breast lesions, and risk of breast cancer may be the result of exposures of breast tissue to both mitogens and mutagens. Characterization of breast density by mammography has several limitations, and the uses of breast density in risk prediction and breast cancer prevention may be improved by other methods of imaging, such as magnetic resonance or ultrasound tomography.

High-Density Lipoprotein-Cholesterol, Daily Estradiol and Progesterone, and Mammographic Density Phenotypes in Premenopausal Women

“…The associations between salivary and serum estradiol (SD) and progesterone (SD) and percent mammographic density (%), stratified by tertiles of HDL-C HDL-C <1.39 increased low-grade inflammation (44), and higher levels of total endogenous estradiol and estradiol locally produced in the breast (44,45). Moreover, immune cells and cytokines may interact in a paracrine manner with ovarian steroids in mammary cells (48), and support the present observation, and the hypothesis that mediators of inflammatory cellular cascades, such as low HDL-C, may influence mammographic density phenotypes (12).…”

“…Mammographic density refers to the structure and relationship of the adipose, epithelial, and stromal tissues (12,13). Percent mammographic density reflects relative amounts of fibroglandular and fat tissue, and absolute mammographic density reflects epithelial and stromal tissues, the dense areas of the breast (14,15).…”

“…Estrogen and progesterone have been observed to induce the proliferation of breast epithelial cells (12), to be associated with HDL-C (21), and with mammographic density (22)(23)(24). Recently, estrogen and mammographic density were observed, independently, to be associated with breast cancer development (25).…”

Breast composition: Measurement and clinical use

“…1 However, it is still contentious whether density is an independent risk factor or merely stimulates other risk factors to cause cancer. Regardless of these contentions, studies have shown that high breast density is associated with a 4-6 fold increased risk of breast cancer, [2][3][4][5] and that a 1% increase in breast density is associated with 2% increase in breast cancer risk. 4 Dense breast tissue has been shown to offer more opportunities for breast cancer to develop, especially in younger women.…”

“…Regardless of these contentions, studies have shown that high breast density is associated with a 4-6 fold increased risk of breast cancer, [2][3][4][5] and that a 1% increase in breast density is associated with 2% increase in breast cancer risk. 4 Dense breast tissue has been shown to offer more opportunities for breast cancer to develop, especially in younger women. 3,[6][7][8] Additionally, there is a genetic predisposition to breast density, 9,10 and other established risk factors for breast cancer such as hormonal agents, 11,12 lifestyle, and reproductive characteristics are associated with high breast density.…”