title: In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.
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.
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, 1151 Richmond St N, London, ON, N6A 5B7, Canada. hamilton@robarts.ca.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Hamilton
authors.affiliation: Imaging Research Laboratories, Robarts Research Institute, 1151 Richmond St N, London, ON, N6A 5B7, Canada.|Department of Medical Biophysics, Schulich School of Medicine & Dentistry, The University of Western Ontario, London, ON, Canada.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Foster
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000000981:diagnostic imaging*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D064726:Triple Negative Breast Neoplasms / Q000000981:diagnostic imaging* / Q000556:secondary*
keywords: Brain metastasis; Experimental mouse model; Magnetic resonance imaging; Triple negative breast cancer