Belgian guidelines for HER2 testing in gastric cancer

1 4 Introduction Human epidermal growth factor receptor 2 (HER2, ErbB2, Neu) is a 185-kDa transmembrane tyrosine kinase receptor. It is a member of the EGFR family and plays a central role in growth factor signal transduction. HER2 overexpression/amplification is implicated in the development of various solid tumours and plays a pivotal role in oncogenic transformation and tumorogenesis.1 The HER2 signaling pathway represents a major therapeutic target. It is well known that, in breast cancer, HER2 overexpression/amplification is associated with aggressive tumour growth, poor prognosis and an increased risk of disease recurrence.2,3 Moreover, in breast cancer, HER2 overexpression/amplification is a predictive marker for targeted therapy with the monoclonal antibody trastuzumab, a fully humanised anti-HER2 monoclonal antibody.4,5 HER2 overexpression, however, has not only been reported in breast cancer, but also in ovarian, lung, endometrium, salivary duct, colon and gastric cancer.6-8 In gastric cancer overexpression/amplification of HER2 were first described already in 1986.9 In conjunction with the knowledge obtained from breast cancer, this leads to experiments to investigate an antitumor effect of anti-HER2 antibodies in gastric cancer. A growth inhibitory effect of trastuzumab was demonstrated in vitro in cultured human gastric tumour cell lines overexpressing HER2 and in vivo in these cell lines growing as xenografts.10 As long ago as 1992, combined chemotherapy (capecitabine/cisplatin) in a xenograft model with trastuzumab Practice Guidelines