Notably, La Marca and Rosen [85] have emphasized the potential role of AREG as a critical estrogen-induced paracrine regulator not only of mammary duct elongation, but also of mammary stem cell self-renewal and differentiation, suggesting that a switch from an ER-mediated, AREG paracrine activity to an autocrine pathway could represent a critical step of mammary carcinogenesis and tumor progression. The gene discussed is ESR1; the disease is neoplasm.