Breast Morphogenesis: From Normal Development to Cancer

The human breast gland is composed of branching epithelial ducts that culminate in milk-producing units known as terminal duct lobular units (TDLUs). The epithelial compartment comprises an inner layer of luminal epithelial cells (LEP) and an outer layer of contractile myoepithelial cells (MEP). Both LEP and MEP arise from a common stem cell population. The epithelial compartment undergoes dynamic branching morphogenesis and remodelling, which expands the surface area for milk production. The epithelial remodelling that starts at the onset of menarche is largely under hormonal control, first and foremost by estrogen and progesterone from ovaries, the production of which is stimulated by pituitary-derived hormones. Menopause leads to a significant decline in estrogen and progesterone levels, resulting in involution and senescence of the breast epithelium. The branching morphogenesis involves developmental events such as epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET). EMT and MET confer plasticity to the epithelial compartment enabling the migration of epithelial cells through the stroma and restoration of the epithelial phenotype. In the normal breast, the stroma, including the basement membrane (BM), collagen-rich extracellular matrix, and various stromal cells, supports the correct histoarchitecture of the glandular tree. However, in cancer, the stroma can acquire tumour-promoting properties and is referred to as the tumour microenvironment. This chapter will explore the developmental processes including branching morphogenesis in the normal breast gland and discuss the lineage relationship between LEPS and MEPs and their interactions with the surrounding stroma in the normal and neoplastic breast gland. Finally, we will review various in vitro and in vivo models employed in mammary gland research.