Location, location, location: regulation of breast cancer progression by the microenvironment

Abstract

The majority of human breast cancers arise from the transformation of epithelial cells. Numerous oncogenic events, including gene amplification, loss, and mutation, have been described that confer a growth-promoting advantage to breast tumors. A classic example of this is the identification of HER-2 amplification in a subset of breast tumors, and the successful use of anti-HER-2 directed therapy in prolonging the survival of patients with breast tumors that have HER-2 amplification. This example clearly highlights the importance of understanding the genetic changes in breast epithelial cells that are associated with breast cancer progression. However, the focus on breast epithelial cell transformation has resulted in the development of several cancer models that ignore another major regulator of breast cancer progression, namely the stroma and microenvironment. Several recent reports from both global gene expression studies and mouse models indicate that the microenvironment may be a critical modulator of breast cancer progression. Given that the microenvironment tends to be more genetically stable than breast tumor cells, it is possible that breast cancer therapies aimed at the microenvironment are less likely to develop acquired resistance. Herein I will briefly highlight several recent papers that show the importance of the microenvironment in regulation of breast cancer progression.