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Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer

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Abstract

Purpose

To evaluate the effect of front-line chemotherapy on CK-19mRNA+ circulating tumor cells (CTCs) and their relevance in patients with metastatic breast cancer (MBC).

Patients and methods

The presence of CK-19mRNA+ CTCs was assessed using a real-time RT-PCR assay in 298 previously untreated patients with MBC before and after the administration of front-line chemotherapy.

Results

CK-19mRNA+ CTCs were detected in the blood of 199 (66.8 %) and 148 (49.7 %) patients before and after chemotherapy, respectively. There was no correlation between the detection of CK-19mRNA+ CTCs after chemotherapy and the various known clinicopathologic parameters except with HER2 status. The incidence of detection of CK-19mRNA+ CTCs was significantly decreased after the administration of 3 (47.8 %; p < 0.001) or 6 (44.3 %; p = 0.001) chemotherapy cycles. The persistent detection of >2.25 CK-19mRNA+ CTCs both before and after chemotherapy (persistently high group) was associated with a significantly (p = 0.003) decreased overall survival. In addition, chemotherapy-induced decrease of CK-19mRNA+ CTCs (≤2.25 CTCs) was associated with a better survival (47 vs 34 months; p < 0.001). Failure of chemotherapy to decrease the CK-19mRNA+ CTCs ≤2.25 was associated with decreased overall survival (HR 1.405, 95 % CI 1.044–1.891; p = 0.025) whereas in multivariate analysis the persistence of >2.25 CTCs both before and after chemotherapy was emerged as an independent prognostic factor (HR 1.661, 95 % CI 1.070–2.579; p = 0.024).

Conclusion

Detection of CK-19mRNA+ CTCs after the completion of front-line chemotherapy in patients with MBC is associated with poor survival and may be a useful tool for the evaluation of front-line chemotherapy.

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Acknowledgments

This work was partly supported by a research grant of the Hellenic Society of Medical Oncology (HESMO) and the Cretan Association for Biomedical Research (CABR).

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, University General Hospital of Heraklion, P.O. Box 1352, Voutes, 71110, Heraklion, Crete, Greece

    V. Georgoulias, V. Bozionelou, K. Kalbakis, A. Kotsakis, A. Xyrafas, S. Agelaki & D. Mavroudis

  2. Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Voutes, 71003, Heraklion, Crete, Greece

    V. Georgoulias, S. Apostolaki, E. Politaki, M. Perraki, N. Georgoulia, A. Kotsakis, S. Agelaki & D. Mavroudis

Authors
  1. V. Georgoulias
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  2. S. Apostolaki
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  3. V. Bozionelou
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  4. E. Politaki
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  5. M. Perraki
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  6. N. Georgoulia
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  9. A. Xyrafas
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  11. D. Mavroudis
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Correspondence to V. Georgoulias.

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Georgoulias, V., Apostolaki, S., Bozionelou, V. et al. Effect of front-line chemotherapy on circulating CK-19 mRNA-positive cells in patients with metastatic breast cancer. Cancer Chemother Pharmacol 74, 1217–1225 (2014). https://doi.org/10.1007/s00280-014-2598-2

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  • DOI: https://doi.org/10.1007/s00280-014-2598-2

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