An overview of mammographic density and its association with breast cancer

Abstract

In 2017, breast cancer became the most commonly diagnosed cancer among women in the US. After lung cancer, breast cancer is the leading cause of cancer-related mortality in women. The breast consists of several components, including milk storage glands, milk ducts made of epithelial cells, adipose tissue, and stromal tissue. Mammographic density (MD) is based on the proportion of stromal, epithelial, and adipose tissue. Women with high MD have more stromal and epithelial cells and less fatty adipose tissue, and are more likely to develop breast cancer in their lifetime compared to women with low MD. Because of this correlation, high MD is an independent risk factor for breast cancer. Further, mammographic screening is less effective in detecting suspicious lesions in dense breast tissue, which can lead to late-stage diagnosis. Molecular differences between dense and non-dense breast tissues explain the underlying biological reasons for why women with dense breasts are at a higher risk for developing breast cancer. The goal of this review is to highlight the current molecular understanding of MD, its association with breast cancer risk, the demographics pertaining to MD, and the environmental factors that modulate MD. Finally, we will review the current legislation regarding the disclosure of MD on a traditional screening mammogram and the supplemental screening options available to women with dense breast tissue.

Keywords: Breast cancer; Dense breast tissue; Extracellular matrix stiffness; Mammographic density; Mammography.

Fig. 1

The visual classification associated with mammographic density [74]. Level 1—breast tissue consisting of entirely adipose tissue with almost no dense tissue. Level 2—scattered density with mostly fat tissue. Level 3—heterogeneous distribution of dense tissue with little fat in the breast tissue. Level 4—highly dense tissue with little to no adipose tissue [74]. (This figure is adapted from an article published by Mayo Clinic with their formal permission to be used in this manuscript)

Fig. 2

An overview of the factors that can modulate mammographic density. a Some of the environmental factors that can affect mammographic density. b A few molecules involved in modulating dense tissue in the breast. HRT hormonal replacement therapy, SLRPs small leucine-rich proteoglycans, TGF-β transforming growth factor-β, COX-2 cyclooxygenase-2, CD36 cluster of differentiation 36