The role of HER2/neu expression and trastuzumab in non-small cell lung cancer

Semin Oncol. 2004 Feb;31(1 Suppl 1):75-82. doi: 10.1053/j.seminoncol.2003.12.018.

Abstract

Research over the past decade has led to an increased understanding of the pathophysiology of lung cancer. The HER2/neu receptor is a member of the ErbB family of signaling-transduction receptors and appears to play a major role in the development of lung cancer as well as many other solid tumors. HER2/neu is overexpressed in 16% to 57% of patients with non-small cell lung cancer (NSCLC) and studies have shown that HER2/neu overexpression imparts a poor prognosis in both resected and advanced NSCLC, as it does in breast cancer. Trastuzumab, a humanized monoclonal antibody that recognizes the HER2/neu protein receptor, has been approved by the US Food and Drug Administration for patients with HER2/neu-positive metastatic breast cancer. In NSCLC preclinical studies, marked synergistic growth inhibition occurred when standard cytotoxic chemotherapy was combined with trastuzumab in HER2/neu-expressing cell lines. In the clinical setting, trastuzumab has proven safe and feasible in combination with cytotoxic chemotherapy in both single-institution and multi-institutional cooperative group studies. Unlike the experience in advanced breast cancer, cardiac toxicity is a marginal concern in this population. However, to date, clinical studies with trastuzumab in patients with NSCLC have not shown a demonstrable advantage for the majority of patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Receptor, ErbB-2 / antagonists & inhibitors*
  • Trastuzumab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Receptor, ErbB-2
  • Trastuzumab