Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 4, pp 685–693 | Cite as

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

  • Antonia Kalykaki
  • Sofia Agelaki
  • Galatea Kallergi
  • Alexandros Xyrafas
  • Dimitris Mavroudis
  • Vassilis Georgoulias
Original Article



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).


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.


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.


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.


Circulating tumor cells Gefitinib Breast cancer EGFR Tyrosine kinase inhibitors 



This work was supported by a grant from Astra Zeneca (UK) and from the Cretan Association for Biomedical Research (CABR).


There is no conflict of interest.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Antonia Kalykaki
    • 1
  • Sofia Agelaki
    • 1
    • 2
  • Galatea Kallergi
    • 2
  • Alexandros Xyrafas
    • 1
  • Dimitris Mavroudis
    • 1
    • 2
  • Vassilis Georgoulias
    • 1
    • 2
  1. 1.Department of Medical OncologyUniversity General Hospital of HeraklionHeraklion, CreteGreece
  2. 2.School of Medicine, Laboratory of Τumor Cell BiologyUniversity of CreteHeraklion, CreteGreece

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