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

Xenidis, Nikolaos; Vlachonikolis, Ioannis G.; Mavroudis, Dimitris; Perraki, Maria; Stathopoulou, Aliki; Malamos, Nikos; Kouroussis, Ch.; Kakolyris, S; Apostolaki, Stella; Vardakis, N.; Lianidou, Evi; Georgoulias, V.

doi:10.1093/annonc/mdg259

Cited by 98 publications

(63 citation statements)

References 28 publications

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“…Since chemotherapy cannot in many cases eliminate the disseminated [29] or/ and the circulating [30] tumor cells, it is important to target these occult tumor cells by using novel therapeutic approaches, such as monoclonal antibodies or other drugs acting on specific molecular targets. In a previous study, the administration of transtuzumab, a humanized anti-HER2 monoclonal antibody, resulted in a significant decrease of the HER2-positive CTCs [22].…”

Section: Discussionmentioning

confidence: 99%

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Apostolaki

Perraki

Kallergi

et al. 2008

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Apostolaki

Perraki

Kallergi

et al. 2008

Breast Cancer Res Treat

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“…The presence of chemoresistant CTCs or DTCs has been previously described (Braun et al, 2000a;Xenidis et al, 2003Xenidis et al, , 2009) and attributed to the low proliferative capacity of these cells (Pantel et al, 1993;Muller et al, 2005). Therefore, it could be hypothesised that the detection of occult tumour cells after the completion of adjuvant chemotherapy could be used as a surrogate marker for the efficacy of the adjuvant treatment used.…”

Section: Discussionmentioning

confidence: 99%

“…Several reports have shown that the persistence of occult tumour cells in the bone marrow (Wiedswang et al, 2004;Janni et al, 2005) or peripheral blood (Xenidis et al, 2003(Xenidis et al, , 2009 after adjuvant chemotherapy or during follow-up is associated with an adverse clinical outcome. In this study, the detection of CTCs and/or DTCs after chemotherapy was not associated with increased risk for relapse or death.…”

Section: Discussionmentioning

confidence: 99%

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Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

et al. 2009

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BACKGROUND: To compare detection rates and evaluate the clinical relevance of cytokeratin-19 (CK-19) mRNA-positive cells in the peripheral blood (circulating tumour cells, CTCs) and bone marrow (disseminated tumour cells; DTCs) of patients with early breast cancer. METHODS: Paired samples of peripheral blood and bone marrow were obtained from 165 patients with stage I -II breast cancer before the initiation of adjuvant chemotherapy. In 84 patients, paired blood and bone marrow samples were also available after chemotherapy. The detection of CK-19 mRNA-positive CTCs and DTCs was assessed by real-time PCR. RESULTS: CK-19 mRNA-positive CTCs and DTCs were detected in 55.2 and 57.6% of patients before chemotherapy, respectively. After chemotherapy, CTCs and DTCs were identified in 44 (52.4%) and 43 (51.2%) of the 84 patients, respectively. There was a 93.9% (McNemar; P ¼ 0.344) and 72.6% (McNemar; P ¼ 0.999) concordance between blood and bone marrow samples before and after chemotherapy, respectively. The detection of CK-19 mRNA-positive CTCs or DTCs before chemotherapy was associated with decreased overall survival (P ¼ 0.024 and P ¼ 0.015, respectively). In addition, their simultaneous detection was also associated with an increased incidence of disease-related death and decreased overall survival (P ¼ 0.016). CONCLUSIONS: The detection of CK-19 mRNA-positive CTCs using reverse transcription-PCR (RT -PCR) both before and after chemotherapy is correlated with the detection of CK-19 mRNA-positive DTCs in patients with early-stage breast cancer. The determination of the CTC status by RT -PCR conveys clinically relevant information that is not inferior to DTC status and, owing to the ease of sampling, warrants further evaluation as a tool for monitoring minimal residual disease.

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“…Studies that investigated the prognostic value of CTCs/DTCs at the time of completion of adjuvant therapy [42, 106,107] showed that the detection of DTCs [42,108] and CTCs [106] after the completion of chemotherapy is associated with an unfavorable clinical outcome [103,105]; further reviewed by Ignatiadis et al [109]. In keeping with this work suggesting diagnostic and prognostic relevance for CK19, more recently full-length CK19 has been detected in bone marrow specimens from breast cancer patients and is associated with the presence of overt metastases and poor survival rates [110].…”

Section: Cytokeratin 19mentioning

confidence: 99%

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

Friel

Corcoran

Crown

et al. 2010

Breast Cancer Res Treat

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Early detection of cancer is vital to improved overall survival rates. At present, evidence is accumulating for the clinical value of detecting occult tumor cells in peripheral blood, plasma, and serum specimens from cancer patients. Both molecular and cellular approaches, which differ in sensitivity and specificity, have been used for such means. Circulating tumor cells and extracellular nucleic acids have been detected within blood, plasma, and sera of cancer patients. As the presence of malignant tumors are clinically determined and/or confirmed upon biopsy procurement-which in itself may have detrimental effects in terms of stimulating cancer progression/metastases-minimally invasive methods would be highly advantageous to the diagnosis and prognosis of breast cancer and the subsequent tailoring of targeted treatments for individuals, if reliable panels of biomarkers suitable for such an approach exist. Herein, we review the current advances made in the detection of such circulating tumor cells and nucleic acids, with particular emphasis on extracellular nucleic acids, specifically extracellular mRNAs and discuss their clinical relevance.

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

Abstract: 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.

Cited by 98 publications

References 28 publications

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Detection of cytokeratin-19 mRNA-positive cells in the peripheral blood and bone marrow of patients with operable breast cancer

Relevance of circulating tumor cells, extracellular nucleic acids, and exosomes in breast cancer

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