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Annals of Oncology 14:849-855, 2003
© 2003 European Society for Medical Oncology


Original Paper

Peripheral blood circulating cytokeratin-19 mRNA-positive cells after the completion of adjuvant chemotherapy in patients with operable breast cancer

N. Xenidis1, I. Vlachonikolis2, D. Mavroudis1, M. Perraki3, A. Stathopoulou4, N. Malamos5, C. Kouroussis1, S. Kakolyris1, S. Apostolaki3, N. Vardakis1, E. Lianidou4 and V. Georgoulias1,3,+

1 Department of Medical Oncology, University General Hospital of Heraklion, Crete; 2 Department of Biostatistics and 3 Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Crete; 4 Department of Analytical Chemistry, Faculty of Chemistry, University of Athens, Athens; 5 Medical Oncology Unit, Marika Heliades Hospital of Athens, Athens, Greece

Received 4 October 2002; revised 20 January 2003; accepted 11 March 2003

Background:

The purpose of this study was to evaluate the prognostic significance of the molecular detection of cytokeratin 19 (CK-19) mRNA-positive cells in the peripheral blood of women with operable breast cancer after the completion of adjuvant chemotherapy.

Patients and methods:

Blood from 161 patients with stage I and II breast cancer, obtained after the completion of adjuvant chemotherapy, was tested by nested RT–PCR for CK-19 mRNA detection. Using univariate and multivariate analyses possible interactions with other prognostic factors and association of CK-19 mRNA detection with risk of relapse, disease-free interval (DFI) and overall survival were investigated.

Results:

After completion of adjuvant chemotherapy, 27.3% of patients had peripheral blood CK-19 mRNA-positive cells; there was no association of this finding with any other prognostic factors or the type of chemotherapy regimen used. For patients with less than four involved axillary lymph nodes the risk of relapse was 3.81 [95% confidence interval (CI) 1.06–13.71] times higher, and the DFI was significantly reduced (P = 0.028) if CK-19 mRNA-positive cells were detectable in the blood after the completion of adjuvant chemotherapy. In contrast, for patients with four or more involved lymph nodes, the presence of CK-19 mRNA-positive cells after adjuvant chemotherapy did not significantly affect the risk of relapse or DFI. Furthermore, the risk of relapse was higher (hazards ratio 3.70; 95% CI 1.09–13.89) and the DFI was reduced (P = 0.022) for patients with detectable CK-19 mRNA-positive cells following adjuvant cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as compared with epirubicin, cyclophosphamide and 5-fluorouracil (FEC) or sequential taxotere–epirubicin and cyclophosphamide (T/EC) chemotherapy.

Conclusions:

The detection of CK-19 mRNA-positive cells in the peripheral blood after adjuvant chemotherapy may be of clinical relevance for patients with early breast cancer and less than four involved axillary lymph nodes.

Key words: adjuvant chemotherapy, blood, breast cancer, CK-19 mRNA


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