Unifying mechanism in the initiation of breast cancer by metabolism of estrogen

Excessive exposure to estrogen is associated with increased risk of breast cancer. The mechanisms of carcinogenesis in the breast caused by estrogen metabolism include formation of depurinating adducts which are released from DNA to generate apurinic sites, and production of reactive oxygen species (ROS). Excess ROS not only exerts genotoxicity by indirectly increasing genomic instability, but also stimulates progression of mammary carcinogenicity by inducing a redox-associated signaling pathway. Estrogen metabolism enzymes serve an important role in estrogen metabolism. Alterations in the expression and activity of estrogen metabolism enzymes may influence estrogen metabolism homeostasis. The present review discusses the process of estrogen metabolism, the role of estrogen metabolites and ROS in breast carcinogenesis, and the effect of metabolism enzyme polymorphisms on generation of pro-carcinogens and breast cancer susceptibility.