ABSTRACT
I. ABSTRACT The elevated breast cancer risk associated with prolonged use of estrogen medications has previously been proposed to be based on uncontrolled stimulation of estrogen receptor (ER)–mediated cell proliferation. More recent evidence from human and animal studies points to an additional role of estrogen as precursor of genotoxic metabolites causing DNA damage. From these more recent data, it has been concluded that the natural hormone estradiol is a weak carcinogen and mutagen and induces tumors, including human breast cancer, by a complex interaction of genotoxic and hormonal effects. This mechanistic possibility of breast cancer induction points to several novel pathways of breast cancer prevention by inhibition of the metabolic activation of estrogen to DNA-reactive intermediates. Breast cancer prevention by modulation of estrogen metabolism remains to be explored in future studies.
