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