The Role of the Hypothalamus-Pituitary-Gonadal Axis in Breast Cancer: a candidate gene approach

This chapter provides a general overview of breast cancer, including the possible role of genetic and exogenous factors and an overview of the role of hormones in carcinogenesis of the breast. Variability in susceptibility to the disease, timing of development, as well as tumor characteristics upon presentation and outcome of breast cancer, are likely to be affected by differences in both genetic and exogenous factors. The role of polymorphic variation in genes involved in hormonal control of carcinogenesis will be introduced. Breast cancer is the most frequently occurring malignancy in women, affecting women of all ages. More than 1 million new cases are diagnosed each year, accounting for almost one third of incident cases of cancer in women in Western industrialized countries . The cumulative lifetime risk, documented between 2000 and 2002, for women in the USA is 13% (1:8), while in The Netherlands the approximate lifetime risk is currently about 11% (1:9) (www.kankerregistratie.nl). In total over 400,000 women die each year worldwide of breast cancer (www.iarc.fr), making it the leading cause of death among women 35 to 55 years of age (3). Important aims of breast cancer research are prevention, early detection and reduction of mortality. Both basic molecular biological research and epidemiological investigations can help to achieve these goals by identification of women at risk, development of techniques for early diagnosis, prediction of outcome and response to therapy and finally optimization of targeted therapies resulting in tailoredtreatment. In essence, breast cancer, like all cancers, is a genetic disease resulting from an accumulation of somatic mutations and/ or altered expression of genes. In addition, breast cancer is a complex, multifactorial disease in which environmental factors and individual genetic background, including germline mutations and polymorphisms, may influence susceptibility, prognosis and response to treatment.

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