Originally published as JCO Early Release 10.1200/JCO.2007.11.7762 on October 22 2007
Journal of Clinical Oncology, Vol 25, No 33 (November 20), 2007: pp. 5194-5202
© 2007 American Society of Clinical Oncology.
Different Prognostic Value of Cytokeratin-19 mRNA–Positive Circulating Tumor Cells According to Estrogen Receptor and HER2 Status in Early-Stage Breast Cancer
Michail Ignatiadis,
Nikos Xenidis,
Maria Perraki,
Stella Apostolaki,
Eleni Politaki,
Maria Kafousi,
Efstathios N. Stathopoulos,
Aliki Stathopoulou,
Evi Lianidou,
Grigorios Chlouverakis,
Christos Sotiriou,
Vassilis Georgoulias,
Dimitris Mavroudis
From the Department of Medical Oncology and Pathology, University General Hospital of Heraklion; Laboratory of Tumor Cell Biology and Department of Biostatistics, School of Medicine, University of Crete, Crete; Laboratory of Analytical Chemistry, Department of Chemistry, University of Athens, Greece; and the Functional Genomics and Translational Research Unit, Jules Bordet Institut, Brussels, Belgium
Address reprint requests to Dimitris Mavroudis, MD, PhD, Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion 711 10, Crete, Greece; e-mail: mavrudis{at}med.uoc.gr
Purpose To examine the prognostic value of cytokeratin-19 (CK-19) mRNA–positive circulating tumor cells (CTCs) in early-stage breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) and HER2 expression.
Patients and Methods CK-19 mRNA–positive CTCs were detected by real-time reverse transcriptase polymerase chain reaction in the blood of 444 consecutive, stage I-III, breast cancer patients before initiation of adjuvant chemotherapy. The association between detection of CK-19 mRNA–positive CTCs and clinical outcome was analyzed for patients with ER-positive, ER-negative, triple-negative, HER2-positive, and ER-positive/HER2-negative tumors.
Results CK-19 mRNA–positive CTCs were detected in 181 (40.8%) of 444 patients; 109 (41.9%) of 260 patients with ER-positive tumors; 71 (40.6%) of 175 patients with ER-negative tumors; 27 (35%) of 77 patients with triple-negative tumors; 35 (39.8%) of 88 patients with HER2-positive tumors; and 82 (44.1%) of 186 patients with ER-positive/HER2-negative tumors. After a median follow-up of 53.5 months, patients with CK-19 mRNA–positive CTCs experienced reduced disease-free survival (DFS; P < .001) and overall survival (OS; P < .001); this was mainly observed in patients with ER-negative (P < .001 and P < .001, respectively) but not ER-positive tumors (P = .172 and P = .425, respectively) and in patients with triple-negative (P = .008 and P = .001, respectively) and HER2-positive (P = .023 and P = .040, respectively) but not ER-positive/HER2-negative tumors (P = .210 and P = .578, respectively). In multivariate analysis, the interaction between CK-19 mRNA–positive CTCs and ER status was the strongest independent prognostic factor for reduced DFS (hazard ratio [HR], 3.808; 95% CI, 2.415 to 6.003; P < .001) and OS (HR, 4.172; 95% CI, 2.477 to 9.161; P < .001).
Conclusion Detection of CK-19 mRNA–positive CTCs before adjuvant chemotherapy predicts poor clinical outcome mainly in patients with ER-negative, triple-negative, and HER2-positive early-stage breast cancer.
published online ahead of print at www.jco.org on October 22, 2007.
M.I. and N.X. have contributed equally to this article.
Authors disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike Complore Connotea Del.icio.us Digg Facebook Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
F.-C. Bidard, Y. M. Kirova, A. Vincent-Salomon, S. Alran, Y. de Rycke, B. Sigal-Zafrani, X. Sastre-Garau, L. Mignot, A. Fourquet, and J.-Y. Pierga
Disseminated tumor cells and the risk of locoregional recurrence in nonmetastatic breast cancer
Ann. Onc.,
November 1, 2009;
20(11):
1836 - 1841.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Mego, U. De Giorgi, L. Hsu, N. T. Ueno, V. Valero, S. Jackson, E. Andreopoulou, S.-W. Kau, J. M. Reuben, and M. Cristofanilli
Circulating tumor cells in metastatic inflammatory breast cancer
Ann. Onc.,
November 1, 2009;
20(11):
1824 - 1828.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Lu, P. S. Steeg, J. E. Price, S. Krishnamurthy, S. A. Mani, J. Reuben, M. Cristofanilli, G. Dontu, L. Bidaut, V. Valero, et al.
Breast Cancer Metastasis: Challenges and Opportunities
Cancer Res.,
June 15, 2009;
69(12):
4951 - 4953.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
N. Xenidis, M. Ignatiadis, S. Apostolaki, M. Perraki, K. Kalbakis, S. Agelaki, E. N. Stathopoulos, G. Chlouverakis, E. Lianidou, S. Kakolyris, et al.
Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer
J. Clin. Oncol.,
May 1, 2009;
27(13):
2177 - 2184.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Ignatiadis, C. Desmedt, C. Sotiriou, E. de Azambuja, and M. Piccart
HER-2 as a Target for Breast Cancer Therapy
Clin. Cancer Res.,
March 15, 2009;
15(6):
1848 - 1852.
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-Y. Pierga, F.-C. Bidard, C. Mathiot, E. Brain, S. Delaloge, S. Giachetti, P. de Cremoux, R. Salmon, A. Vincent-Salomon, and M. Marty
Circulating Tumor Cell Detection Predicts Early Metastatic Relapse After Neoadjuvant Chemotherapy in Large Operable and Locally Advanced Breast Cancer in a Phase II Randomized Trial
Clin. Cancer Res.,
November 1, 2008;
14(21):
7004 - 7010.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Alix-Panabieres, S. Riethdorf, and K. Pantel
Circulating Tumor Cells and Bone Marrow Micrometastasis
Clin. Cancer Res.,
August 15, 2008;
14(16):
5013 - 5021.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F.-C. Bidard, A. Vincent-Salomon, S. Gomme, C. Nos, Y. de Rycke, J. P. Thiery, B. Sigal-Zafrani, L. Mignot, X. Sastre-Garau, J.-Y. Pierga, et al.
Disseminated Tumor Cells of Breast Cancer Patients: A Strong Prognostic Factor for Distant and Local Relapse
Clin. Cancer Res.,
June 1, 2008;
14(11):
3306 - 3311.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Ignatiadis, G. Kallergi, M. Ntoulia, M. Perraki, S. Apostolaki, M. Kafousi, G. Chlouverakis, E. Stathopoulos, E. Lianidou, V. Georgoulias, et al.
Prognostic Value of the Molecular Detection of Circulating Tumor Cells Using a Multimarker Reverse Transcription-PCR Assay for Cytokeratin 19, Mammaglobin A, and HER2 in Early Breast Cancer
Clin. Cancer Res.,
May 1, 2008;
14(9):
2593 - 2600.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A Vincent-Salomon, F C Bidard, and J Y Pierga
Bone marrow micrometastasis in breast cancer: review of detection methods, prognostic impact and biological issues
J. Clin. Pathol.,
May 1, 2008;
61(5):
570 - 576.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|