Aspects of genetic and clinical heterogeneity in breast cancer in breast cancer

Breast cancer affects approximately 1 in every 12 women in Western countries. It is the leading cause of cancer death in women in these countries. Investigation of the mechanism of breast carcinogenesis is hampered by the heterogeneity of the disease that can be observed at the clinical, biological and genetic levels. Delineating this heterogeneity may give opportunities to gain more insight in the cellular mechanisms that lead to breast cancer. It may also be clinically helpful, by allowing diagnostic screening programmes to women at risk, and facilitating estimates of prognosis and the design of rational therapies adjusted to specific subgroups. This thesis describes attempts to analyse various aspects of breast cancer heterogeneity from a phenotypic as well as from a genotypic point of view. Genetic alterations are the fundamental changes that lead to cancer initiation and progression. Many genetic alterations have been observed in breast cancer and some of these changes could cause differences in histopathology of the tumour and in the clinical outcome of the disease. Our research therefore focussed on linking specific genetic events to subtypes of breast tumours or to an increased breast cancer risk.