Elimination of EGFR-expressing circulating tumor cells in patients with metastatic breast cancer treated with gefitinib

Cancer Chemother Pharmacol. 2014 Apr;73(4):685-93. doi: 10.1007/s00280-014-2387-y. Epub 2014 Feb 4.


Purpose: The purpose of the study is to evaluate the effect of gefitinib, an anti-EGFR TKI on circulating tumor cells (CTCs) in patients with metastatic breast cancer (MBC).

Methods: Seventeen patients with MBC with detectable CTCs after the completion of prior treatment received gefitinib 250 mg/day p.o. CTCs were monitored by immunofluorescence microscopy after double staining with anti-cytokeratin (A45-B/B3) and either anti-CD45 or anti-EGFR antibodies.

Results: A median reduction of 96.4 and 94.1 % in CTC count was observed in 11 (64.7 %) and 12 (70.6 %) of patients after the first and the second treatment cycles, respectively. Total CTC numbers declined by 73 and 44 % after the first and second treatment cycles, respectively. In nine patients with EGFR(+)/CK(+) CTCs, gefitinib resulted in a reduction of both EGFR(+) and EGFR(-) CTCs, and after the third course, most detected CTCs were EGFR(-). In two patients, with a sustained decrease in CTC numbers, a PFS of 16.0 and 19.0 months was observed and in one of them, it was associated with clinical objective response.

Conclusion: Treatment-resistant CTCs could be eliminated by gefitinib in MBC, and EGFR expression on CTCs merits further validation as a potential biomarker for specific and effective targeting of CTCs.

Trial registration: ClinicalTrials.gov NCT00428896.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • ErbB Receptors / biosynthesis*
  • Female
  • Gefitinib
  • Humans
  • Microscopy, Fluorescence
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplastic Cells, Circulating / drug effects*
  • Neoplastic Cells, Circulating / metabolism*
  • Neoplastic Cells, Circulating / pathology
  • Quinazolines / therapeutic use*


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Quinazolines
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib

Associated data

  • ClinicalTrials.gov/NCT00428896