Prospect for anti-HER2 receptor therapy in breast cancer.

ABSTRACT

The carcinogenesis process is characterized, in part, by the dysfunction of cellular communication pathways, such as the one involving HER2. HER2 is a member of the EGF receptor family, which participates in cell growth and proliferation. HER2 may be overexpressed in 15 to 30% of breast cancer cases and is associated with poor prognosis, shortened overall survival and shorter time to disease progression. Furthermore, an increasing number of studies have demonstrated the relevance of HER2 serum concentrations (sHER2, extracellular domain released into blood by proteolysis) as a predictive marker of resistance to chemotherapy in HER2-overexpressing metastatic breast cancer. The determination of HER2 overexpression/ amplification in the diagnosis of relapse of breast cancer is currently a routine procedure. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) techniques, which are used to detect HER2 expression in the tumor, are improving constantly, and other parallel techniques such as chromogenic in situ hybridization (CISH) are starting to emerge. sHER2 concentrations can be measured using ELISA techniques, which can be automated. All of these procedures still need to be standardized. The discovery of a monoclonal antibody (4D5) that can inhibit the growth and proliferation of cells overexpressing HER2 led to the development of trastuzumab. Like 4D5, trastuzumab recognizes an epitope on the extracellular domain of HER2. Moreover, trastuzumab is also able to stimulate antibody-dependent cellular toxicity (ADCC). It is administered alone or in combination (with navelbine, taxol, carboplatin...) in patients with metastatic breast cancer overexpressing HER2. Other active antibodies have since been discovered, as well as other specific molecules, such as tyrosine kinase inhibitors which will undoubtedly find a place in the therapeutic arsenal used in breast cancer, especially to avoid the emergence of resistance to treatment.