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Metastatic Determinants: Breast Tumour Cells in Circulation

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Cell and Molecular Biology of Breast Cancer

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Abstract

More than 90 % of deaths from breast cancer are a result of metastases, rather than the primary tumour. In recent years it has become possible to study the occult steps of metastasis that have previously been clinically undetectable—single tumour cells that have disseminated early on from the primary tumour and are en route to distant sites. High-resolution genomic and gene analyses of these rare cells show that they carry their own unique sets of aberrations and are frequently quite different from the primary tumours they originated from. They appear to be heterogeneous and in a transitional state, expressing genes necessary to allow them passage into the circulation as well as genes required to see them through survival or dormancy in blood vessels and metastatic niches such as the bone marrow and lymph nodes. They possess gene signatures ranging from up-regulation of genes associated with invasiveness and dormancy to expression of favourable growth factor receptors that facilitate extravasation and survival at secondary sites. Circulating tumour cells (CTCs) in the blood and disseminated tumour cells (DTCs) in the bone marrow have been reported to have strong prognostic relevance by predicting survival and relapse in both early and late stages of breast cancer. They are emerging as promising biomarkers for monitoring the response to treatment, whereby a drop in cell numbers is suggestive of a positive response, but persisting cells indicate resistance and a poor prognosis. It is apparent that not just the primary and metastatic tumours need to be targeted, but also the intermediate cells in transition that do not necessarily reflect the genetics of the tumour they originated from or the metastasis they may eventually give rise to. As more disseminated cell markers are being consecutively added to a growing panel, the heterogeneous nature of breast cancer is becoming more evident, paving the way for a systemic approach to experimental design and treatment regimens. Molecular characterization of single disseminated cells in the bloodstream will help address many of the questions surrounding the development of breast cancer metastasis.

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Authors and Affiliations

  1. The Campbell Family Institute for Breast Cancer Research, 620 University Avenue, Suite 7-504, Toronto, ON, Canada, M5G 2M9

    Nisha Kanwar & Susan J. Done

Authors
  1. Nisha Kanwar
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  2. Susan J. Done
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Correspondence to Susan J. Done .

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Editors and Affiliations

  1. University of Missouri-Columbia Dept. Veterinary Pathobiology, Columbia, Missouri, USA

    Heide Schatten

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Kanwar, N., Done, S.J. (2013). Metastatic Determinants: Breast Tumour Cells in Circulation. In: Schatten, H. (eds) Cell and Molecular Biology of Breast Cancer. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-634-4_10

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