HERe-2 Stay: The Continuing Importance of Translational Research in Breast Cancer

Extract

This issue of the Journal contains two important articles that discuss human epidermal growth factor receptor 2 (HER2), also known as c-erbB2 or neu, as a therapeutic target in breast cancer (1,2). The first details preclinical studies that examine the combination of trastuzumab with a number of chemotherapeutic agents. The second applies the knowledge learned in the preclinical studies to the clinical setting and the treatment of patients with HER2-positive metastatic breast cancer. These studies are important with regard to what they tell us about HER2-positive breast cancer and its treatment and about a style of research. All have important implications.

HER2 is a member of a family of transmembrane receptor tyrosine kinases. To summarize more than two decades of research, HER2 lacks a functioning ligand-binding domain yet represents the preferred dimerization partner for other members of the EGFR family (3,4). Since the late 1980s, HER2 has been known to be overexpressed in the tumors of approximately 20% of patients with breast cancer. Overexpression is typically a consequence of amplification at the DNA level (measurable in the clinic by fluorescence in situ hybridization [FISH]) and is associated with an increased risk of relapse and death for patients with early-stage breast cancer (5). The poor prognosis is the clinical manifestation of the many biologic actions of HER2: increased proliferation, increased cell survival, increased invasion and metastasis, and increased angiogenic activity (6,7).