A developing breast tumor is regulated by its tumor microenvironment (TME) which includes various immune cell subsets, fibroblasts, adipocytes, and endothelial and epithelial cells surrounded by an extracellular matrix (ECM). Breast tissue density is also a defining feature of breast cancer and plays an integral role in the exchange of biochemical cues between cells and the ECM. Cell signals from these interactions regulate tumor growth, metabolism, immunity, and invasion. The distinct organization of cells in the ECM generates structural patterns that are important in understanding disease development and progression. In this chapter, we discuss this complex interplay between the ECM and cells in the TME. Various models that mimic density are described to more fully understand the effect of ECM density on immunity, metabolism, tumorigenesis, and dormancy. Continued study of the interactions between cells and the ECM in the TME may provide needed biomarkers and therapeutic targets in breast cancer.
Keywords: Breast cancer; Collagen; Dormancy; Mammographic density; Mechanotransduction; Metabolism; Metastasis; Migration; Tumor immunity; Tumor-associated collagen signatures (TACS).