Annals of Oncology Advance Access published online on May 21, 2007
Annals of Oncology, doi:10.1093/annonc/mdm208
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© 2007 European Society for Medical Oncology
Clinical relevance of circulating CK-19 mRNA-positive cells detected during the adjuvant tamoxifen treatment in patients with early breast cancer
1 Department of Medical Oncology,University General Hospital of Heraklion, Crete
2 Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion
3 Department of Pathology, University General Hospital of Heraklion, Crete
4 Department of Medical Oncology, University General Hospital of Alexandroupolis, Alexandroupolis, Greece
* Correspondence to: Dr V. Georgoulias, Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, 711 10 Heraklion, Crete, Greece. Tel: +30-2810-392823; Fax: +30-2810-392802; E-mail: georgsec{at}med.uoc.gr
Background: The purpose of this study was to evaluate the effect of adjuvant treatment with tamoxifen on the CK-19 mRNA+ cells in patients with early-stage breast cancer.
Patients and methods: CK-19 mRNA+ cells were prospectively and longitudinally detected using a specific real-time PCR assay for CK-19 mRNA in 119 patients with estrogen and/or progesterone receptor-positive tumors during the period of tamoxifen administration.
Results: Twenty-two (18.5%) patients had detectable CK-19 mRNA+ cells after the completion of adjuvant chemotherapy and in 15 (68.2%) of them adjuvant tamoxifen could not eliminate these cells (persistently positive). In 68 (57.1%) patients, no CK-19 mRNA+ cells could be detected throughout the follow-up period (persistently negative). Seven (46.7%) of the 15 persistently positive and six (8.8%) of the 68 persistently negative patients developed disease recurrence (P = 0.00026). Persistency of CK-19 mRNA+ cells was associated with a significantly lower median disease-free interval (P = 0.0001) and overall survival (P = 0.0005). Multivariate analysis revealed that the detection of CK-19 mRNA+ cells during the administration of tamoxifen was associated with an increased risk of relapse [hazard ratio (HR) = 22.318, P = 0.00006] and death (HR = 13.954, P < 0.00001).
Conclusions: The detection of CK-19 mRNA+ cells throughout the period of adjuvant tamoxifen treatment is an independent poor prognostic factor in patients with early breast cancer.
breast cancer, circulating tumor cells, CK-19, tamoxifen
Received for publication December 11, 2006. Revision received March 21, 2007. Accepted for publication April 25, 2007.
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