Targeting the Human Epidermal Growth Factor Receptor 2 in Esophageal Cancer

Abstract

The importance of human epidermal growth factor-2 (HER2) in terms of prognosis and aggressiveness of growth has long been known in breast cancer, and interruption of its growth cascade by agents such as trastuzumab and lapatinib has markedly improved outcomes for these patients with HER2 overexpression. HER2 overexpression also occurs in many other tumor types, including esophageal cancer. In this disease, a different scoring system for determining overexpression is used. Limited data exist concerning the biological and therapeutic implications of HER2 overexpression in esophageal cancer. One trial, the so-called ToGA trial, included patients with advanced gastric and gastroesophageal junction (GEJ) tumors that overexpressed HER2. Patients who received trastuzumab plus cisplatin-based chemotherapy had more responses and longer progression-free and overall survival than those who received the chemotherapy alone. Enthusiasm concerning these results must be tempered by the facts that only 25% of the study group had GEJ tumors and, of these, only 33% had HER2 overexpression. Thus, the role of trastuzumab in the management of HER2-overexpressing esophageal cancers remains to be determined. In addition to presenting data on the HER2 cascade, the authors review clinical trials performed to date and also present the validated standard scoring system for HER2 overexpression in esophageal cancer.