Figure 2

Breast cancer originates in undifferentiated terminal structures of the mammary gland (Lobules type 1) that contain Stem cells 1, the target of the neoplastic event. Early parity induces differentiation of the mammary gland, creating Stem cells 2. Even though differentiation significantly reduces cell proliferation in the mammary gland, the mammary epithelium remains capable of responding with proliferation to given stimuli, such as a new pregnancy. Under these circumstances, however, the cells that are stimulated to proliferate are from structures that have already been primed by the first cycle of differentiation, that are able to metabolize the carcinogen and repair the induced DNA damage more efficiently than the cells of the nulliparous gland, and that are less susceptible to carcinogenesis. However, if the shifting of Stem cells 1 to Stem cells 2 has not been completed, a powerful enough carcinogenic stimulus may overburden the system, thereby initiating successfully a neoplastic process.