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Clinical application of circulating tumor cells in breast cancer

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Abstract

Circulating tumor cells (CTCs) play a major role in the metastatic spread of breast cancer. CTC detection has proven to be an important parameter for predicting progression free and overall survival. Collection of CTCs is minimally invasive and can be performed more often than disseminated tumor cell (DTC) collection from bone marrow, thus providing a real-time “liquid biopsy”. In this review, the most important techniques for enrichment and detection of CTCs are discussed for clinical application in low and higher staged breast cancer, as well as the genetic and molecular characterization of CTCs. For CTCs, the use of immunology-based enrichment techniques with multiple antibodies is recommended in a clinical setting, as well as the use of cytometric detection techniques, combined with RT-PCR for confirmation. Special attention is given to the value of cancer stem cell (CSC) activity, which may be the main cause of ineffectiveness of the control over metastatic lesions due to intratumor heterogeneity. Accumulating information on CSCs offers new paradigms to generate effective targets for the treatment of metastatic disease. Genetic and molecular characterization of CTCs has potential to stratify patients for optimal personalized treatment regimens. CTCs can be used for monitoring patients during treatment schedules.

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Abbreviations

CK:

Cytokeratin

CSC:

Cancer stem cell

CTC:

Circulating tumor cell

DTC:

Disseminated tumor cell

ELISPOT:

Enzyme-linked immunospot

EMT:

Epithelial-to-mesenchymal transition

EpCAM:

Epithelial cell adhesion molecule

EPISPOT:

Epithelial immunospot assay

FISH:

Fluorescence in situ hybridization

ICC:

Immunocytochemistry

ISET:

Isolation by size of epithelial tumor cells

PCR:

Polymerase chain reaction

PFS:

Progression free survival

RT-PCR:

Reverse transcription polymerase chain reaction

OS:

Overall survival

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Surgery, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC, Leiden, The Netherlands

    Leonie H. A. Broersen, Gabi W. van Pelt, Rob A. E. M. Tollenaar & Wilma E. Mesker

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  1. Leonie H. A. Broersen
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  2. Gabi W. van Pelt
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  3. Rob A. E. M. Tollenaar
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  4. Wilma E. Mesker
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Correspondence to Wilma E. Mesker.

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Broersen, L.H.A., van Pelt, G.W., Tollenaar, R.A.E.M. et al. Clinical application of circulating tumor cells in breast cancer. Cell Oncol. 37, 9–15 (2014). https://doi.org/10.1007/s13402-013-0160-6

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