Abstract 2699: Glucocorticoid receptor biology in lobular breast cancer

Abstract

Abstract While considered uncommon, there are an estimated 39,000 new invasive lobular carcinoma (ILC) cases in the US yearly, making it the sixth most common among all tumor types. ILC is recognized for unique metastatic organotropism. Its propensity to metastasize to serosal surfaces lining the gut (peritoneum) and lung (pleura) make it particularly challenging to diagnose and consequently is associated with overall unfavorable prognosis. We hypothesize that GR activation will slow cell proliferation and reduce metastatic potential of ILC cells in vitro and in vivo. Using transcriptome data from 142 ILC tumors with long-term follow up clinical data from the METABRIC dataset we found a trend towards improved overall patient survival with increased GR (NR3C1) expression (and presumably activity). Preliminary in vitro data showed slowed cell proliferation in an ILC cell line (MDA-MB-134IV) treated with GR agonist dexamethasone relative to vehicle control. ILC cell lines (MDA-MB-134IV and SUM44PE) have dramatically different adhesion preference for extracellular components and we will study whether GR mediates the metastatic organotrophism of ILC cells. Preliminary transcriptome data lends insight into the proliferative and adhesive gene expression changes elicited by both ER and GR activation. Two GR+ ILC patient derived organoid lines have GR dependent proliferative and adhesive phenotypes. In future studies we will utilize an in vivo mouse model that recapitulates ILC progression from an in situ to invasive breast carcinoma and finally to metastatic colonization of distant organs to determine the role of GR activity in proliferation and metastasis to the serosal surfaces. Citation Format: Candace Frerich, Ishrat Durdana, Ariella Hanker, Carlos L. Arteaga, Lynda Bennett, Suzanne Conzen. Glucocorticoid receptor biology in lobular breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2699.