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In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer

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Abstract

Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

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Acknowledgements

PJF received funding for this research from the Canadian Institutes of Health Research. Operating grant number # MOP 130447. We thank Dr. Patricia Steeg, Deputy Chief, Women’s Malignancies Branch, Center for Cancer Research at the National Cancer Institute, Bethesda, Maryland for providing the 231-BR and 4T1-BR5 cell lines.

Funding

PJF received funding for this research from the Canadian Health Institute of Research. Operating grant number # MOP 130447.

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Authors and Affiliations

  1. Imaging Research Laboratories, Robarts Research Institute, 1151 Richmond St N, London, ON, N6A 5B7, Canada

    Amanda M. Hamilton & Paula J. Foster

  2. Department of Medical Biophysics, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada

    Paula J. Foster

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  1. Amanda M. Hamilton
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Correspondence to Amanda M. Hamilton.

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AMH declares no conflict of interest.

Research Involving Human Participants and/or Animals

All applicable international, national and institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standards of the institution at which the studies were conducted. This article does not contain any studies with human participants performed by any of the authors.

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Hamilton, A.M., Foster, P.J. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer. Clin Exp Metastasis 34, 133–140 (2017). https://doi.org/10.1007/s10585-016-9835-5

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  • DOI: https://doi.org/10.1007/s10585-016-9835-5

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