Understanding susceptibility to breast cancer metastasis: the genetic approach.

Metastasis is a complex phenotype that is not discrete, is polygenic, varies in range over the entire population and follows non-Mendelian inheritance. Recent evidence indicates that inherited susceptibility affects not only the development of the primary tumor, but is also an important factor in progression and metastasis. Since metastasis accounts for the majority of breast cancer deaths, identification and understanding of the genetic modifiers of metastasis underlies success of personalized therapy. Studies from our laboratory and others have now characterized several metastasis susceptibility factors. While an important step forward, these certainly do not describe the entire metastatic phenomenon and efforts continue to expand this knowledge. Here we review the complex metastatic process and current knowledge on the genetics of breast cancer metastasis, including germline polymorphisms that have been associated with the disease.