Breast Cancer - Recent Advances in Biology, Imaging and Therapeutics

Abstract

Approximately 20 to 30 % of all breast cancer cases are classified as HER2/neu-positive (McCann et al. 1991). The overexpression the HER2 receptor tyrosine kinase is most commonly caused by a gene amplification and is associated with aggressive tumor behavior (Hynes & Stern 1994). Patients with HER2/neu overexpressing tumors have a significantly shorter time to relapse as well as a reduced overall survival rate compared to patients with normal HER2/neu expression levels (Berchuck et al. 1990; Slamon et al. 1989; Slamon et al. 1987). The oncogenic properties of HER2/neu were first discovered in rat neuroblastoma (“neu”) as a tumor antigen related to epidermal growth-factor receptor (EGFR) (Schechter et al. 1984). The human homologue to neu was mapped to chromosome 17q21 and, because of its similarity to the human EGF receptor, named human EGF receptor 2 (HER2) (Coussens et al. 1985; King et al. 1985). Two more members of the HER family, namely HER3 and HER4, were subsequently identified (Kraus et al. 1989; Plowman et al. 1993). In this review we will discuss the altered metabolism and potential downstream effects found in breast cancer cells with increased HER2/neu expression.