Genomic and molecular classification of breast cancer

At present, the biology of breast cancer remains poorly understood. Currently, lymph node metastases, tumor grade, and size, and expression of hormone receptors provide the only true prognostic and predictive factors related to clinical outcome and response to treatment, respectively. Many other potential candidates have been suggested but, due to their limited predictive power, have not been widely accepted by the general oncological community. These histopathological features do not allow us any insight into breast cancer biology, however, and these prognostic classifications are far from perfect. At present, due to these limitations many clinicians consider prescribing adjuvant treatment to many women with early breast cancer to reduce the risk of relapse, only to benefit a few, thus exposing many patients to unnecessary toxicity. Since the publication of the complete sequence of the human genome however, a new era of research has begun [1]. More than 3 billions base pairs form the 30,000-40,000 genes that code all the required genetic information of a particular individual. The functions of the vast majority of these genes are still unknown. A combination of circumstances, including the advent of array-based technology and progress in the human genome initiative, have provided the ideal opportunity to begin efforts aimed at performing comprehensive molecular and genetic profiling of human cancers. The ability to interrogate tens of thousands of genes simultaneously by using microarray technologies has significantly changed our approach to the analysis of expression profiles, and has also led to an increased understanding of the basic biology of breast cancer. Such comprehensive technologies permit the assessment not only of individual genes, but also of clusters of genes that are coordinately expressed to generate "fingerprints" of biological states of the cells of origin. This is especially important given that it has become increasingly evident that the biology of cancer, particularly solid tumors, is determined by the behavior of many genes, rather than a few. Although there are other techniques that analyze differences in gene expression, none matches the ease and the comprehensive nature of the interrogation associated with c-DNA- or oligonucleotide-based microarray analysis. A list of the terms commonly used in this field is given in Table 30.1. (Table presented). © Springer-Verlag Berlin Heidelberg 2006.SCOPUS: ch.b