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Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications

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Abstract

Breast cancer that has metastasized to the brain presents difficult clinical challenges. This diagnosis comes with high mortality rates, largely due to complexities in early detection and ineffective therapies associated with both dormancy and impermeability of the blood–brain barrier (BBB). Magnetic resonance imaging (MRI) is the current gold standard for diagnosis and assessment of brain tumors. It has been used clinically to investigate metastatic development as well as monitor response to therapy. Here, we describe preclinical imaging strategies that we have used to study the development of brain metastases due to breast cancer. Using this approach, we have identified three subsets of metastatic disease: permeable metastases, nonpermeable metastases, and solitary, dormant cancer cells, which likely have very different biology and responses to therapy. The ability to simultaneously monitor the spatial and temporal distribution of dormant cancer cells, metastatic growth, and associated tumor permeability can provide great insight into factors that contribute to malignant proliferation. Our preclinical findings suggest that standard clinical detection strategies may underestimate the true metastatic burden of breast cancer that has metastasized to the brain. A better understanding of true metastatic burden in brains will be important to assist in the development of more effective chemotherapeutics—particularly those targeted to cross the BBB—as well as detection of small nonpermeable metastases.

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Acknowledgments

We thank Chelsey Gareau for preparation of Fig. 4. Work described in this review is supported by a grant from the US Department of Defense Breast Cancer Research Program (#W81XWH-06–2-0033). DBP is supported by studentships from the Canadian Institutes of Health Research Strategic Training Program in Cancer Research and Technology and the Translational Breast Cancer Research Unit of the London Regional Cancer Program. AFC is Canada Research Chair in Oncology and receives salary support from the Canada Research Chairs Program.

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Authors and Affiliations

  1. Department of Medical Biophysics, Western University, London, ON, Canada

    Donna H. Murrell, Paula J. Foster & Ann F. Chambers

  2. Imaging Research Laboratories, Robarts Research Institute, London, ON, Canada

    Donna H. Murrell & Paula J. Foster

  3. London Regional Cancer Program, 790 Commissioners Road East, London, ON, Canada, N6A 4 L6

    Ann F. Chambers

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  1. Donna H. Murrell
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Correspondence to Ann F. Chambers.

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Murrell, D.H., Foster, P.J. & Chambers, A.F. Brain metastases from breast cancer: lessons from experimental magnetic resonance imaging studies and clinical implications. J Mol Med 92, 5–12 (2014). https://doi.org/10.1007/s00109-013-1108-z

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