Estrogens, Estrogen Receptor and Breast Cancer
Estrogens have been implicated to play a role in the development of breast cancer. The purpose of this book is to provide a comprehensive analysis of experimental, clinical, and epidemiological evidence in support of the carcinogenicity of estrogens. The book is organized into seven chapters with the first one providing a historical review. The second chapter analyzes estrogen synthesis and metabolism based on the recent molecular and pharmacogenetic characterization of enzymes that determine estrogen levels in the breast. The next chapter is devoted to the molecular endocrinology of the estrogen receptors alpha and beta, including recent insights into the crystallographic structure and the interaction with coactivators, cointegrators and chromatin. Chapter four addresses physiological effects of estrogens on development, differentiation, and the cell cycle, that are pertinent to breast cancer. Pathological effects resulting in the formation of estrogen-DNA adducts from catechol estrogen intermediates are reviewed as part of experimental carcinogenesis. The rest remaining chapters describe the clinical correlates of estrogen receptor expression in breast cancer with emphasis on practical aspects of receptor status determination, abnormalities of the estrogen receptor gene, mRNA, and protein, and the utility of the receptor as marker of hormone dependence and prognostic indicator. A detailed analysis of other tumour markers and their relation to estrogen receptor in breast cancer is presented with emphasis on clinical relevance. The role of endogenous estrogens as breast cancer risk factor as well as the risk associated with exogenous estrogens in form of oral contraceptives and estrogen replacement therapy is analysed. The potential roles of phytoestrogens and xenoestrogens are also discussed. Finally, an unified model of breast cancer development in presented which takes into account the latest findings in molecular epidemiology, pharmacogenetics, and experimental biology.