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The clinical significance of disseminated tumor cells in breast cancer

Nature Clinical Practice Oncology volume 4, pages 30–41 (2007)Cite this article

Abstract

The presence of tumor cells in the bone marrow of primary breast cancer patients at surgery has been shown to be an independent prognostic indicator of relapse. Tumor cells have been detected either directly, using immunocytochemical staining, or indirectly, using reverse transcription–polymerase chain reaction (RT-PCR). Studies have been initiated to determine whether the presence of disseminated cells can be monitored during the therapy of patients with primary breast cancer, and thus potentially be used to predict relapse before overt metastases are detectable. Studies are also ongoing to improve methods of detection, such as immunobead enrichment followed by staining and real-time RT-PCR, and to find alternative markers for the disseminated cells. Studies of patients with overt metastases have shown that there is a large tumor load in the peripheral blood and that this predicts overall survival. This article reviews the published literature on studies carried out in both primary and metastatic breast cancer patients, the methodologies and markers used, and improvements in detection methodologies that are being investigated including real-time RT-PCR, novel markers, enrichment and automated image analysis.

Key Points

  • On the basis of the pooled analysis of 4,703 patients, it is evident that the presence of micrometastases at surgery is an independent prognostic indicator of relapse in primary breast cancer

  • Cytokeratins are to date the best markers for detecting micrometastases by immunocytochemistry

  • RT-PCR has been demonstrated to be superior to immunocytochemistry in terms of sensitivity, but more-specific markers are required before this method can replace immunocytochemistry as the standard methodology

  • Standardized methodologies are required for detecting and monitoring micrometastases before they can be used as a basis for therapeutic change

  • Monitoring micrometastases in primary breast cancer patients currently requires the analysis of bone marrow aspirates, but new techniques/methodologies will potentially result in the use of peripheral blood, and will consequently lead to this being adopted as standard practice in breast cancer management

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Figure 1: Disseminated tumor cells stained with A45B/B3 antibody for pan-cytokeratin detected using alkaline phosphatase, showing a cluster of disseminated tumor cells against a background of lymphocytes counterstained with hematoxylin and eosin.

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Acknowledgements

The authors would like to thank The Breast Cancer Research Trust, Cancer Research (UK) and the European Union for funding this research. The authors would also like to thank Mr Gopichand Tripuraneni for his contributions to this manuscript.

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  1. at the Department of Oncology, Division of Surgery, MJ Slade is a research fellow, and RC Coombes is a clinical professor, Oncology, Reproductive Biology and Anaesthetics (SORA), Faculty of Medicine, Imperial College, London, UK.,

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Correspondence to Martin J Slade.

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Slade, M., Coombes, R. The clinical significance of disseminated tumor cells in breast cancer. Nat Rev Clin Oncol 4, 30–41 (2007). https://doi.org/10.1038/ncponc0685

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