Original Article

Cancer Chemotherapy and Pharmacology

, Volume 73, Issue 4, pp 685-693

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

  • Antonia KalykakiAffiliated withDepartment of Medical Oncology, University General Hospital of Heraklion
  • , Sofia AgelakiAffiliated withDepartment of Medical Oncology, University General Hospital of HeraklionSchool of Medicine, Laboratory of Τumor Cell Biology, University of Crete
  • , Galatea KallergiAffiliated withSchool of Medicine, Laboratory of Τumor Cell Biology, University of Crete
  • , Alexandros XyrafasAffiliated withDepartment of Medical Oncology, University General Hospital of Heraklion
  • , Dimitris MavroudisAffiliated withDepartment of Medical Oncology, University General Hospital of HeraklionSchool of Medicine, Laboratory of Τumor Cell Biology, University of Crete
  • , Vassilis GeorgouliasAffiliated withDepartment of Medical Oncology, University General Hospital of HeraklionSchool of Medicine, Laboratory of Τumor Cell Biology, University of Crete Email author 

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Abstract

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.

Keywords

Circulating tumor cells Gefitinib Breast cancer EGFR Tyrosine kinase inhibitors