After extensive family history of breast cancer, mammographic density is the strongest risk factor for the development of breast cancer.  Women with dense breasts have 4 times the likelihood of developing breast cancer compared to women without dense breasts. It is also well known that breast tissue density increases in about 25%-30% of women who begin hormone replacement therapy and that, conversely, breast density decreases in some women who are placed on tamoxifen or raloxifene.
The authors have shown that single-nucleotide polymorphisms (SNPs) in the IGF pathway are related to risk of mammographically dense breasts and that the relation of mammographic density to increased breast cancer risk is independent of circulating hormone levels.  These findings suggest long-term energy balance may operate to modify breast density and requires further evaluation of energy balance and the microbiome to refine our understanding.