Towards an understanding of breast cancer etiology

We present an etiological model for breast cancer in humans, and we examine whether it accommodates the patterns of occurrence of this disease and the associated risk factors. The model has four components: (1) the likelihood of breast cancer occurrence depends on the number of cells at risk; (2) the number of target cells is partially determined early in life, perhaps even in utero; (3) while a pregnancy stimulates the replication of already initiated cells, it conveys long-term protection through structural changes, terminal cellular differentiation, and perhaps other mechanisms; and (4) in adult life, mammotropic hormones, in conjunction with their receptors, affect the number of target cells, the likelihood of retention of spontaneous somatic mutations, and the rate of expansion of initiated clones. The model accommodates several hypotheses but also allows new insights.