This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Smith, B. M. Articles by Coombes, R. C. Search for Related Content PubMed PubMed Citation Articles by Smith, B. M. Articles by Coombes, R. C. Social Bookmarking                            What's this?

Response of Circulating Tumor Cells to Systemic Therapy in Patients With Metastatic Breast Cancer: Comparison of Quantitative Polymerase Chain Reaction and Immunocytochemical Techniques

From the Cancer Research Campaign Laboratories, Division of Cancer Cell Biology, and Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital; and Department of Surgery, Charing Cross Hospital, London, United Kingdom.

Address reprint requests to Martin J. Slade, PhD, Cancer Research Campaign Laboratories, Division of Cancer Cell Biology, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 ONN, United Kingdom; email m.slade{at}ic.ac.uk

PURPOSE: We previously developed a quantitative system for the detection of cytokeratin 19 (CK-19) transcripts using reverse transcriptase polymerase chain reaction (PCR) to detect breast carcinoma cells in blood and bone marrow. The aim of this study was to determine the value of this system in monitoring patients with metastatic disease and to compare it with an established immunocytochemical method.

PATIENTS AND METHODS: Patients with progressive, locally advanced, and metastatic breast cancer (all stage IV) who were due to start systemic treatment were recruited. Blood samples were analyzed for CK-19 transcripts using quantitative PCR (QPCR) and immunocytochemistry (ICC) throughout their course of treatment.

RESULTS: One hundred forty-five blood samples were obtained from 22 patients over 13 months. Seventy-two (49.6%) of these samples were positive by QPCR, and 56 (42%) of 133 were positive by ICC. Of the 133 specimens analyzed by both techniques, 95 (71.4%) had the same results for each, and of the 71 samples that were positive, 40 (56%) were positive by both methods. The relationship between the number of cells detected and the QPCR values was statistically significant (P < .0001). Of the 25 courses of assessable treatment, 17 (68%) of 25 treatment outcomes (either response or disease progression) were reflected by QPCR measurements, and 12 (57%) of 21 were reflected by ICC. During the course of the study, five patients showed a response, and of these, ICC was in agreement in four cases (80%) and QPCR in three cases (60%). Eighteen courses of treatment resulted in progression of the disease; however, only 15 of these were assessable by ICC. ICC was in agreement in eight (53%) of 15 of these cases, and QPCR in 15 (83%) of 18 cases.

CONCLUSION: Circulating carcinoma cells are frequently found in patients with metastatic breast cancer. In the majority of patients, cancer cell numbers as evaluated by QPCR or ICC reflected the outcome of systemic treatment.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				L. R. Jiao, C. Apostolopoulos, J. Jacob, R. Szydlo, N. Johnson, N. Tsim, N. A. Habib, R. C. Coombes, and J. Stebbing Unique Localization of Circulating Tumor Cells in Patients With Hepatic Metastases J. Clin. Oncol., December 20, 2009; 27(36): 6160 - 6165. [Abstract] [Full Text] [PDF]

				E. Dotan, S. J. Cohen, K. R. Alpaugh, and N. J. Meropol Circulating Tumor Cells: Evolving Evidence and Future Challenges Oncologist, November 1, 2009; 14(11): 1070 - 1082. [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]

				K. Pantel, C. Alix-Panabieres, and S. Riethdorf Circulating Tumor Cells: Detection and Clinical Relevance Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 603 - 610. [Abstract] [Full Text] [PDF]

				L. Harris, H. Fritsche, R. Mennel, L. Norton, P. Ravdin, S. Taube, M. R. Somerfield, D. F. Hayes, and R. C. Bast Jr American Society of Clinical Oncology 2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer J. Clin. Oncol., November 20, 2007; 25(33): 5287 - 5312. [Abstract] [Full Text] [PDF]

				M. Lacroix Significance, detection and markers of disseminated breast cancer cells Endocr. Relat. Cancer, December 1, 2006; 13(4): 1033 - 1067. [Abstract] [Full Text] [PDF]

				P. Wulfing, J. Borchard, H. Buerger, S. Heidl, K. S. Zanker, L. Kiesel, and B. Brandt HER2-Positive Circulating Tumor Cells Indicate Poor Clinical Outcome in Stage I to III Breast Cancer Patients. Clin. Cancer Res., March 15, 2006; 12(6): 1715 - 1720. [Abstract] [Full Text] [PDF]

				V. Muller, N. Stahmann, S. Riethdorf, T. Rau, T. Zabel, A. Goetz, F. Janicke, and K. Pantel Circulating Tumor Cells in Breast Cancer: Correlation to Bone Marrow Micrometastases, Heterogeneous Response to Systemic Therapy and Low Proliferative Activity Clin. Cancer Res., May 15, 2005; 11(10): 3678 - 3685. [Abstract] [Full Text] [PDF]

				V. Bozionellou, D. Mavroudis, M. Perraki, S. Papadopoulos, S. Apostolaki, E. Stathopoulos, A. Stathopoulou, E. Lianidou, and V. Georgoulias Trastuzumab Administration Can Effectively Target Chemotherapy-Resistant Cytokeratin-19 Messenger RNA-Positive Tumor Cells in the Peripheral Blood and Bone Marrow of Patients With Breast Cancer Clin. Cancer Res., December 15, 2004; 10(24): 8185 - 8194. [Abstract] [Full Text] [PDF]

				J.-Y. Pierga, C. Bonneton, A. Vincent-Salomon, P. de Cremoux, C. Nos, N. Blin, P. Pouillart, J.-P. Thiery, and H. Magdelenat Clinical Significance of Immunocytochemical Detection of Tumor Cells Using Digital Microscopy in Peripheral Blood and Bone Marrow of Breast Cancer Patients Clin. Cancer Res., February 15, 2004; 10(4): 1392 - 1400. [Abstract] [Full Text] [PDF]

				K. Pantel, V. Muller, M. Auer, N. Nusser, N. Harbeck, and S. Braun Detection and Clinical Implications of Early Systemic Tumor Cell Dissemination in Breast Cancer Clin. Cancer Res., December 15, 2003; 9(17): 6326 - 6334. [Abstract] [Full Text] [PDF]

				M. K. Baker, K. Mikhitarian, W. Osta, K. Callahan, R. Hoda, F. Brescia, R. Kneuper-Hall, M. Mitas, D. J. Cole, and W. E. Gillanders Molecular Detection of Breast Cancer Cells in the Peripheral Blood of Advanced-Stage Breast Cancer Patients Using Multimarker Real-Time Reverse Transcription-Polymerase Chain Reaction and a Novel Porous Barrier Density Gradient Centrifugation Technology Clin. Cancer Res., October 15, 2003; 9(13): 4865 - 4871. [Abstract] [Full Text] [PDF]

				M. S. Ismail, W. Wynendaele, J. L. E. Aerts, R. Paridaens, L. Van Mellaert, J. Anne, R. Gaafar, N. Shakankiry, H. M. Khaled, M. R. Christiaens, et al. Real-time quantitative RT-PCR and detection of tumour cell dissemination in breast cancer patients: plasmid versus cell line dilutions Ann. Onc., August 1, 2003; 14(8): 1241 - 1245. [Abstract] [Full Text] [PDF]

				R. A. Wascher, K. T. Huynh, A. E. Giuliano, N. M. Hansen, F. R. Singer, D. Elashoff, and D. S. B. Hoon Stanniocalcin-1: A Novel Molecular Blood and Bone Marrow Marker for Human Breast Cancer Clin. Cancer Res., April 1, 2003; 9(4): 1427 - 1435. [Abstract] [Full Text] [PDF]

				J.-C. Goeminne, T. Guillaume, M. Federico, R. Sabbatini, M. Morselli, R. Depenni, K. Cagossi, M. Luppi, G. Torelli, and V. Silingardi Detection of Circulating Tumor by Reverse Transcriptase Polymerase Chain Reaction J. Clin. Oncol., September 17, 2000; 18(17): 3196 - 3197. [Full Text] [PDF]