Chapter 3: Endogenous Estrogens as Carcinogens Through Metabolic Activation

A common thread linking the main risks for developing breast cancer in women is cumulative, excessive exposure to estrogen. The standard paradigm to account for this asso-ciation focuses on increased cell proliferation caused by es-trogen through estrogen receptor-mediated signal transduc-tion accompanied by increased probability for mutation to occur during DNA synthesis. This chapter provides an over-view of the mounting evidence, provided from cell culture and whole animal experimental studies, in support of a role for the oxidative metabolites of estrogen, in particular, the catechol estrogens, in the development of estrogen carcino-genesis. This provides a paradigm for how estrogens may contribute to the development of human breast cancer. The chapters that follow will fill in the details. Evidence shows that the catechols themselves are signaling molecules tha