Abstract
Abstract Inflammatory Breast Cancer (IBC) is a rare form of breast cancer, accounting for approximately 2% of all breast cancer cases worldwide. While rare, it is extremely progressive and has a high propensity for metastatic spread and decreased overall survival compared to non-IBC breast cancers. IBC has a five-year overall survival rate of 30%; the median age at diagnosis is 57 years of age. Approximately 15% of IBC patients develop brain metastasis, and most of the brain metastasizing IBC tumors are triple negative (ER-, PR- and HER2-) or Her-2 overexpressing. The goal of this study was to investigate the neuroinflammatory response of SUM190 cells, a Her-2 overexpressing IBC cell line, in a mouse model of brain metastasis. The SUM190 brain metastatic mouse model of IBC was developed following three-sequential rounds of injection of cells into the left cardiac ventricle, isolation of metastatic tumor cells from the brains of the mice, and growth in tissue culture to maintain brain metastatic potential of the cell line. In this model, brain metastases were widely disseminated throughout the neuroparenchyma. The lesions were round, and measured 0.5-1 mm in maximal diameter, with a central area of necrosis characterized by shrunken hypereosinophilic epithelial cells with karryorhectic or absent nuclei. There was no significant difference in vascular proliferation in the peritumoral microenvironment compared to the unaffected neuroparenchyma (p=0.57) following quantitative immunofluorescent analysis. However, there was a 4-fold increase in GFAP-positive astrocytes (p=<0.0001) and CD11b-positive microglia (p=0.001) and a 3-fold increase in F4/80-positive macrophages (p=0.001) in the tumor microenvironment compared to the unaffected neuroparenchyma. CD3+ T cells were widely disseminated throughout the tumor microenvironment. The influx of inflammatory cells in brain metastases associated with IBC is greater than that of other brain-tropic breast cancer cell lines including MDA-MB-231-BR, and may explain the increased incidence of metastasis in IBC patients. This research was supported by the NIH Intramural Research Program and a grant from the Inflammatory Breast Cancer Research Foundation. Citation Format: L. Tiffany Reed, Diane Palmieri, Ginny Mason, Patricia Steeg. Characterization of the neuroinflammatory response in a mouse model of brain metastatic inflammatory breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4976. doi:10.1158/1538-7445.AM2013-4976
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