HER-2/neu Amplification Association with Clinical Outcome of Breast Cancer in Thailand

The HER-2/neu oncogene (c-erbB-2) is a member of the epidermal growth factor receptor family and encodes a 185-kDa transmembrane glycoprotein with tyrosine kinase activity (Schechter et al., 1984; Akiyama et al., 1986). HER-2/neu is mapped to the long arm of chromosome 17 (17q21) (Muleris et al., 1997) and its protein product is involved in signal transduction (Yarden, 2001; Marmor et al., 2004). Amplification of the HER-2/neu gene, and overexpression of its receptor protein, are found in about 20-30% of breast cancers (Slamon et al., 1989; Owens et al., 2004; Ross et al., 2004). A monoclonal antibody, trastuzumab, was developed to target HER-2/neu, as a novel therapy for breast-cancer patients. Several studies of human breast cancer have recently demonstrated the clinical benefits of trastuzumab after chemotherapy, with significant overall survival benefits over chemotherapy alone (Slamon et al., 2001; Piccart-Gebhart et al., 2005; Romond et al., 2005; Smith et al., 2007). HER-2/neu amplification has also been shown to correlate with a poor prognosis (Slamon et al., 1987; Borg et al., 1994; Press et al., 1997; Révillion et al., 1998; Carr et al., 2000; Riou et al., 2001), and with resistance to conventional adjuvant chemotherapy and tamoxifen (Borg et al., 1994; Carlomagno et al., 1996; Têtu et al.,