Tissue density in the progression of breast cancer: Bedside to bench and back again.

Women with high breast density are at notably greater risk for breast cancer. Moreover, breast tumor tissue can be up to 10-fold stiffer than normal tissue, containing dense extracellular matrix (ECM) proteins. This density affects numerous aspects of breast cancer progression, and as such is critical to patient diagnosis and treatment. Here, we review recent advances in using engineered models to understand the ramifications of dense breast tissue for tumor progression. Matrix density has been found to influence immune cell infiltration and stromal components of the tumor microenvironment, including fibroblast activation and tumor angiogenesis. Use of engineered scaffolds has also revealed that changing tissue density alters breast cancer metabolism. Going forward, the complexity and specificity of tissue-engineered scaffolds that more closely mimic the physiological breast microenvironment will continue to be developed, potentially even tailored to individual patients. A challenge going forward is the leveraging of these novel tools and knowledge gained about breast density to identify therapeutic targets to treat breast cancer.