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The significance of circulating epithelial cells in Breast Cancer patients by a novel negative selection method

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Abstract

Purpose: A negative selection method for the enumeration and characterization of circulating epithelial/cancer cells (CCC) in Breast Cancer (BC) patients is described. This manual procedure yields reproducible results of high sensitivity and selectivity suitable for research laboratories. Patients and methods: We conducted a prospective blood sampling study in 105 women with stage 1–4 BC attending clinics at the University of Maryland Greenebaum Cancer Center to define the prevalence of CCC utilizing our sensitive double gradient centrifugation and magnetic cell sorting CCC detection and enumeration method. CCC were isolated and enumerated from 15 to 20 ml of venous blood drawn before the start of systemic therapy and periodically thereafter for up to 24 months. One or more CCC/sample was considered a positive result. Results: We analyzed 487samples for the presence of CCC; the median number of samples/patient was 4 (range 1–8). CCC were detected in 56% of patients, 19%—stage 1; 43%—stage 2; 46%—stage 3; 83%—stage 4. The probability of being positive for the presence of CCC is significantly associated with the stage of cancer (P < 0.0001). The frequency of CCC positive patients and samples increased with the advancing stage of disease. Presence of more than 10 CCC/sample was associated with the decreased survival and increased probability of having metastatic disease P = 0.001. Conclusions: Increasing number of CCC/sample correlates with the adverse outcome and poorer survival (P < 0.0001). Our CCC test based on the negative selection procedure may provide valuable prognostic information.

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Acknowledgement

The work done at CCC Diagnostics LLC is supported by NCI Grant #CA081903.

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Authors and Affiliations

  1. University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 S Greene St. S9D12, Baltimore, MD, 21201, USA

    Katherine H. Rak Tkaczuk, Olga Goloubeva, Nancy S. Tait, Faye Feldman & Ming Tan

  2. CCC Diagnostics, LLC, 3918 Vero Road, Suite B, Baltimore, MD, USA

    Zhao-Ping Lum, Stephen A. Lesko, David A. Van Echo & Paul O. P. Ts’o

Authors
  1. Katherine H. Rak Tkaczuk
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  2. Olga Goloubeva
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  3. Nancy S. Tait
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  4. Faye Feldman
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  5. Ming Tan
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  6. Zhao-Ping Lum
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  7. Stephen A. Lesko
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  8. David A. Van Echo
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  9. Paul O. P. Ts’o
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Corresponding author

Correspondence to Katherine H. Rak Tkaczuk.

Additional information

Partly presented at the 41st and 42nd Annual Meeting of the American Society of Clinical Oncology, May 2005, Orlando, FL, USA and June, 2006, Atlanta, GA, USA.

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Tkaczuk, K.H.R., Goloubeva, O., Tait, N.S. et al. The significance of circulating epithelial cells in Breast Cancer patients by a novel negative selection method. Breast Cancer Res Treat 111, 355–364 (2008). https://doi.org/10.1007/s10549-007-9771-9

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  • DOI: https://doi.org/10.1007/s10549-007-9771-9

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