Hypotheses. (a) Schematic summary. We postulate that the combined effects of cell proliferation (mitogenesis) and genetic damage to proliferating cells caused by mutagens (mutagenesis) may underlie the increased risk for breast cancer associated with extensive mammographic density. Mitogenesis and mutagenesis are related processes. Increased cell proliferation increases susceptibility to mutations but also increases lipid peroxidation, which can in turn increase cell proliferation (see text). (b) Biological hypothesis. The tissue components (epithelial cells, stromal cells, collagen and fat) that are responsible for variations in mammographic density are related to each other in several ways. Stromal fibroblasts produce collagen, and some are pre-adiopocytes that differentiate into adipocytes. Stromal and epithelial cells influence each other through paracrine growth factors, and both cell types are influenced by endocrine stimuli to cell proliferation (mitogenesis). Genetic damage to either stromal or epithelial cells caused by mutagens (mutagenesis) could initiate carcinogenesis (see text).