This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hayes, D. F. Articles by Terstappen, L. W.W.M. Search for Related Content PubMed PubMed Citation Articles by Hayes, D. F. Articles by Terstappen, L. W.W.M.

Circulating Tumor Cells at Each Follow-up Time Point during Therapy of Metastatic Breast Cancer Patients Predict Progression-Free and Overall Survival

Authors' Affiliations: ¹ Department of Internal Medicine and the Comprehensive Cancer Center, University of Michigan Health and Hospital System, Ann Arbor, Michigan; ² Department of Breast Medical Oncology, M.D. Anderson Cancer Center, Houston, Texas; ³ Department of Medicine, Cleveland Clinic Foundation, Cleveland, Ohio; ⁴ Department of Medicine, Washington University, St. Louis, Missouri; ⁵ Department of Medicine, Arizona Cancer Center, Tucson, Arizona; and ⁶ Immunicon Corp., Huntingdon Valley, Pennsylvania

Requests for reprints: Daniel F. Hayes, University of Michigan, 6312 CCGC, 1500 East Medical Center Drive, Ann Arbor, MI 48109. Phone: 734-615-6725; Fax: 734-615-3947; E-mail: hayesdf{at}umich.edu.

Purpose: We reported previously that 5 circulating tumor cells (CTC) in 7.5 mL blood at baseline and at first follow-up in 177 patients with metastatic breast cancer (MBC) were associated with poor clinical outcome. In this study, additional follow-up data and CTC levels at subsequent follow-up visits were evaluated.

Experimental Design: CTCs were enumerated in 177 MBC patients before the initiation of a new course of therapy (baseline) and 3 to 5, 6 to 8, 9 to 14, and 15 to 20 weeks after the initiation of therapy. Progression-free survival (PFS) and overall survival (OS) times were calculated from the dates of each follow-up blood draw. Kaplan-Meier plots and survival analyses were done using a threshold of 5 CTCs/7.5 mL at each blood draw.

Results: Median PFS times for patients with <5 CTC from each of the five blood draw time points were 7.0, 6.1, 5.6, 7.0, and 6.0 months, respectively. For patients with 5 CTC, median PFS from these same time points was significantly shorter: 2.7, 1.3, 1.4, 3.0, and 3.6 months, respectively. Median OS for patients with <5 CTC from the five blood draw time points was all >18.5 months. For patients with 5 CTC, median OS from these same time points was significantly shorter: 10.9, 6.3, 6.3, 6.6, and 6.7 months, respectively. Median PFS and OS times at baseline and up to 9 to 14 weeks after the initiation of therapy were statistically significantly different.

Conclusions: Detection of elevated CTCs at any time during therapy is an accurate indication of subsequent rapid disease progression and mortality for MBC patients.

This article has been cited by other articles:

				J. S. de Bono, H. I. Scher, R. B. Montgomery, C. Parker, M. C. Miller, H. Tissing, G. V. Doyle, L. W.W.M. Terstappen, K. J. Pienta, and D. Raghavan Circulating Tumor Cells Predict Survival Benefit from Treatment in Metastatic Castration-Resistant Prostate Cancer Clin. Cancer Res., October 1, 2008; 14(19): 6302 - 6309. [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]

				D. Olmos, H.-T. Arkenau, J. E. Ang, I. Ledaki, G. Attard, C. P. Carden, A. H. M. Reid, R. A'Hern, P. C. Fong, N. B. Oomen, et al. Circulating tumour cell (CTC) counts as intermediate end points in castration-resistant prostate cancer (CRPC): a single-centre experience Ann. Onc., August 11, 2008; (2008) mdn544v1. [Abstract] [Full Text] [PDF]

				J.-P. Eliane, M. Repollet, K. E. Luker, M. Brown, J. M. Rae, G. Dontu, A. F. Schott, M. Wicha, G. V. Doyle, D. F. Hayes, et al. Monitoring Serial Changes in Circulating Human Breast Cancer Cells in Murine Xenograft Models Cancer Res., July 15, 2008; 68(14): 5529 - 5532. [Abstract] [Full Text] [PDF]

				D. F. Hayes and J. Smerage Is There a Role for Circulating Tumor Cells in the Management of Breast Cancer? Clin. Cancer Res., June 15, 2008; 14(12): 3646 - 3650. [Abstract] [Full Text] [PDF]

				A. O. Abdalla, P. Kokhaei, L. Hansson, H. Mellstedt, and A. Osterborg Idiotype vaccination in patients with myeloma reduced circulating myeloma cells (CMC) Ann. Onc., June 1, 2008; 19(6): 1172 - 1179. [Abstract] [Full Text] [PDF]

				F. Nole, E. Munzone, L. Zorzino, I. Minchella, M. Salvatici, E. Botteri, M. Medici, E. Verri, L. Adamoli, N. Rotmensz, et al. Variation of circulating tumor cell levels during treatment of metastatic breast cancer: prognostic and therapeutic implications Ann. Onc., May 1, 2008; 19(5): 891 - 897. [Abstract] [Full Text] [PDF]

				J. Sastre, M. L. Maestro, J. Puente, S. Veganzones, R. Alfonso, S. Rafael, J. A. Garcia-Saenz, M. Vidaurreta, M. Martin, M. Arroyo, et al. Circulating tumor cells in colorectal cancer: correlation with clinical and pathological variables Ann. Onc., May 1, 2008; 19(5): 935 - 938. [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]

				M C. Miller, G. V Doyle, and L. W M M Terstappen Monitoring and Characterization of CTC in Cancer Patients Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 617 - 624. [Abstract] [Full Text] [PDF]

				L. Pusztai Current Status of Prognostic Profiling in Breast Cancer Oncologist, April 1, 2008; 13(4): 350 - 360. [Abstract] [Full Text] [PDF]

				F.-C. Bidard, A. Vincent-Salomon, B. Sigal-Zafrani, V. Dieras, C. Mathiot, L. Mignot, J.-P. Thiery, X. Sastre-Garau, and J.-Y. Pierga Prognosis of women with stage IV breast cancer depends on detection of circulating tumor cells rather than disseminated tumor cells Ann. Onc., March 1, 2008; 19(3): 496 - 500. [Abstract] [Full Text] [PDF]

				C. P. Carden, D. Olmos, and J. S. de Bono Validated and Qualified Biomarkers Are Critical to Optimizing Anticancer Drug Development: Potential Roles for the Study of Circulating Tumor Cells ASCO Educational Book, January 1, 2008; 2008(1): 166 - 170. [Abstract] [Full Text] [PDF]

				A. Stojadinovic, E. A. Mittendorf, J. P. Holmes, A. Amin, M. T. Hueman, S. Ponniah, and G. E. Peoples Quantification and Phenotypic Characterization of Circulating Tumor Cells for Monitoring Response to a Preventive HER2/neu Vaccine-Based Immunotherapy for Breast Cancer: A Pilot Study Ann. Surg. Oncol., December 1, 2007; 14(12): 3359 - 3368. [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]

				T. Nakagawa, S. R. Martinez, Y. Goto, K. Koyanagi, M. Kitago, T. Shingai, D. A. Elashoff, X. Ye, F. R. Singer, A. E. Giuliano, et al. Detection of Circulating Tumor Cells in Early-Stage Breast Cancer Metastasis to Axillary Lymph Nodes Clin. Cancer Res., July 15, 2007; 13(14): 4105 - 4110. [Abstract] [Full Text] [PDF]

				L. Xi, D. G. Nicastri, T. El-Hefnawy, S. J. Hughes, J. D. Luketich, and T. E. Godfrey Optimal Markers for Real-Time Quantitative Reverse Transcription PCR Detection of Circulating Tumor Cells from Melanoma, Breast, Colon, Esophageal, Head and Neck, and Lung Cancers Clin. Chem., July 1, 2007; 53(7): 1206 - 1215. [Abstract] [Full Text] [PDF]

				D. R. Shaffer, M. A. Leversha, D. C. Danila, O. Lin, R. Gonzalez-Espinoza, B. Gu, A. Anand, K. Smith, P. Maslak, G. V. Doyle, et al. Circulating Tumor Cell Analysis in Patients with Progressive Castration-Resistant Prostate Cancer Clin. Cancer Res., April 1, 2007; 13(7): 2023 - 2029. [Abstract] [Full Text] [PDF]

				S. Riethdorf, H. Fritsche, V. Muller, T. Rau, C. Schindlbeck, B. Rack, W. Janni, C. Coith, K. Beck, F. Janicke, et al. Detection of Circulating Tumor Cells in Peripheral Blood of Patients with Metastatic Breast Cancer: A Validation Study of the CellSearch System Clin. Cancer Res., February 1, 2007; 13(3): 920 - 928. [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]