Breast cancer metastasis-associated genes: prognostic significance and therapeutic implications

The metastatic spread of breast cancer accounts for most of its morbidity and mortality; therefore, identifying the genes and gene products involved in breast cancer metastasis formation should be useful for better diagnosis, prognosis, treatment, and follow-up of patients with metastatic breast cancer. Unfortunately, little is known about these genes or the functions of their encoded products. Abnormalities in at least three broad gene categories (oncogenes, regulatory genes or effector genes, and tumor-suppressor genes) have been shown to contribute to the origin and/or progression of breast neoplasias. Such abnormalities are mainly manifested by quantitative changes in gene expression, resulting in loss of normal cellular regulation and enhanced cellular diversification. In addition, qualitative genetic alterations, such as gene amplifications and mutations, may also be involved in breast cancer progression. The role(s) of different breast cancer metastasis-associated genes, if known, in the complex multistep process of invasion and metastasis is discussed along with studies that have identified new molecular probe(s) that may be useful in predicting metastasis formation and outcome in breast cancer and for selecting candidates for adjuvant therapy. Understanding the genetic and thus molecular basis of metastasis formation should also provide important insights on the development of new therapeutic approaches for treatment of metastatic breast cancers based on gene targeting and repair of genetic defects that control metastatic properties.