Genetic alterations in breast cancer

The development of neoplasms is the result of the accumulation of genetic alterations. In breast cancer, large efforts have been dedicated to unravel these genetic alterations and to find associations between specific genetic alterations and the clinical and pathological characteristics of the tumour. There has been rapid advancement of the available techniques to identify new genetic alterations; technical advancement will also place the detection of genetic alterations in breast carcinomas within the grasp of routine clinical testing. As tumour behaviour is largely determined by these genetic alterations, it is to be expected that clinical decision-making in the future will be increasingly influenced by knowledge of the genetic make-up of a tumour. In breast cancer, the main genetic alterations are amplification of approximately 10 oncogenes and inactivation of an unknown number of tumour suppressor genes. In addition, germline mutations in the BRCA1 and 2 genes account for genetic predisposition to develop breast and ovarian cancer. The histological tumour type has been shown to be associated with the presence of specific genetic alterations: for example, inactivation of E-cadherin is specific for the development of lobular breast cancer; HER2 (c-erb B2) gene amplification is associated with poorly differentiated ductal cancer; and tumours in patients with BRCA1 and 2 germline mutations are often poorly differentiated ductal cancers. Also, associations between specific genetic alterations and clinical behaviour (i.e. metastating potential and sensitivity to systemic treatment) are starting to emerge.