Closing remarks and treatment guidelines

The human epidermal growth factor receptor HER2 or C-erbB-2/neu is a tyrosi ne kinase membrane receptor, which when activated, induces a phosphorylatio n cascade in cytoplasmic kinases leading to increased protein transcription and cellular growth. HER2 plays an important role in the biology of breast cancer, an observation that has led to the selection of HER2 as a potentia l target for breast cancer treatment. Trastuzumab (Herceptin(R)) is the fir st anti-HER2 monoclonal antibody that has shown a survival benefit in metas tatic breast cancer patients with HER2-positive rumours (Norton et al., Pro c ASCO 2000 18, 127a (abstract 483)). Tumour HER2 status should no longer b e ignored because of its direct implications for the optimal management of breast cancer patients. A high priority for future research is to refine an d standardise HER2 testing in order to minimise false-negative results. Fur thermore, this procedure would overcome current issues relating to test rep roducibility between pathology laboratories and definitions of HER2 positiv ity. In the meantime, a HER2-positive status on testing using any approved technique has implications for clinical practice (Fig. 1). The treatment al gorithm given in Fig. 1 considers the lack of level 1, evidence-based studi es that demonstrate convincingly the value of HER2 as a predictive marker f or resistance or sensitivity to classic forms of breast cancer therapy (Pic cart et al., Eur J Cancer 2000, 36, 1755-1761). In addition, the algorithm incorporates the available data from 1999-2000, which were generated from p rospective trials exploring the value of trastuzumab both as a single agent and in combination with chemotherapy. (C) 2001 Published by Elsevier Scien ce Ltd.