Epidermal growth factor receptor as a potential therapeutic target in triple-negative breast cancer

Ann Oncol. 2009 May;20(5):862-7. doi: 10.1093/annonc/mdn710. Epub 2009 Jan 15.


Background: No proven targeted therapy is currently available for the treatment of triple-negative breast cancer (TNBC). Epidermal growth factor receptor (EGFR) is frequently overexpressed in TNBC. We studied the activity of EGFR antagonists alone, and in combination with chemotherapy, in TNBC cell lines.

Materials and methods: EGFR and phosphorylated EGFR were measured by enzyme-linked immunosorbent assay. Sensitivity to EGFR inhibitors alone and in combination with chemotherapy was assessed. Effects of gefitinib on EGFR signalling and cell cycle were also examined.

Results: EGFR was overexpressed in the TNBC compared with the human epidermal growth factor receptor 2 (HER-2)-positive cell lines. Phosphorylation of EGFR was detected in the TNBC cells in response to epidermal growth factor stimulation and was blocked by gefitinib treatment. However, the TNBC cell lines were less sensitive to EGFR inhibition than the HER-2-positive cell lines. Response to gefitinib was associated with reduced phosphorylation of both mitogen activated protein kinase (MAPK) and Akt and induction of G(1) arrest. Gefitinib enhanced response to both carboplatin and docetaxel in the TNBC cells, and the triple combination of gefitinib, carboplatin and docetaxel was synergistic.

Conclusions: Although the TNBC cells are less sensitive to EGFR inhibition than the HER-2-positive cell lines, gefitinib enhanced response to chemotherapy. Gefitinib combined with carboplatin and docetaxel warrants further investigation in TNBC.

Publication types

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

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Carboplatin / pharmacology
  • Cell Cycle / drug effects
  • Cell Line, Tumor
  • Docetaxel
  • Dose-Response Relationship, Drug
  • Down-Regulation
  • Drug Synergism
  • ErbB Receptors / antagonists & inhibitors*
  • ErbB Receptors / metabolism
  • Female
  • Gefitinib
  • Humans
  • Inhibitory Concentration 50
  • Mitogen-Activated Protein Kinases / metabolism
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Quinazolines / pharmacology*
  • Receptor, ErbB-2 / metabolism*
  • Receptors, Estrogen / metabolism*
  • Receptors, Progesterone / metabolism*
  • Signal Transduction / drug effects*
  • Taxoids / pharmacology


  • Protein Kinase Inhibitors
  • Quinazolines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Taxoids
  • Docetaxel
  • Carboplatin
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • Receptor, ErbB-2
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinases
  • Gefitinib