Early life events and conditions and breast cancer risk: from epidemiology to etiology.

Risk factors for breast cancer--documented by intensive epidemiological investigations and viewed in the context of general principles of carcinogenesis--can be integrated to an etiologic model comprising 3 principal components: the likelihood of breast cancer occurrence depends on the number of mammary tissue-specific stem cells, which is determined in early life; all growth-enhancing mammotropic hormones affect the rate of expansion of initiated clones; and while a pregnancy stimulates the replication of already initiated cells, it conveys long-term protection through differentiation of mammary tissue-specific stem cells. This perspective accommodates much of what is known about the epidemiology and natural history of breast cancer and highlights the role of early life in the origin of this cancer.