The Distinctive Nature of HER2-Positive Breast Cancers

Abstract

Breast cancer is not a single disease but a group of several important tumor subtypes, each with a different natural history and each requiring a different treatment. Overexpression of HER2 (which derives its name from human epidermal growth factor receptor 2) defines one of these unique subtypes. The HER2/neu gene is a member of a family of genes encoding transmembrane receptors for growth factors, including the epidermal growth factor receptor (EGFR), HER2, HER3, and HER4. The intracellular domain of HER2 has tyrosine kinase activity that regulates important aspects of the physiology, growth, and differentiation of cells.^1,2 Extracellular domains of the HER2 protein interact with HER family members, allowing HER2 to serve as a coreceptor and to facilitate signal transduction as part of a heterodimer complex that forms after ligand binding. There is no known ligand for HER2 itself, however, suggesting that the primary role of HER2 is to modulate signals after ligand binding to other HER-family receptors.