Abstract 5283: Glucocorticoid receptor (GR) activity alters invasive lobular breast cancer (ILC) oncogenic properties

Abstract Invasive breast cancer (BC) is commonly divided into two subtypes, invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC). ILC makes up 10-15% of all BC cases. Expression of nuclear hormone receptors further define clinical histology and directs treatment; receptors include estrogen (ER), progesterone (PR), androgen (AR), and glucocorticoid receptors (GR). Tumor GR expression activation is associated with good prognosis in ER+ but poor prognosis in ER- BC. The majority of ILC tumors are ER+, and we have found that GR expression in primary ILC tumors correlates with improved overall survival. We hypothesized that GR activity in ILC may play a role in ILC’s indolent natural history and could alter its metastatic tendency. We used two isogenic ILC cell lines, each with and without GR expression (MM134-GR+/GR- and SUM44PE-GR+/GR-) to study GR-mediated ILC associated phenotypes. Specifically, we describe GR’s effect on proliferation in vitro and tumor formation in the in vivo MIND model. We also measured GR-mediated ILC adherence to major components of the extra cellular matrix (collagen I, collagen II, laminin, fibronectin, vitronectin, and tenascin). To recapitulate early metastasis, we examined ILC cell movement through a 10 uM microchannel device. We found that GR expression and activation in ILC cell lines cause decreased cell proliferation and decreased adherence to laminin. Preliminary experiments suggest that GR activation altered ILC cell’s ability to enter and navigate through restrictive 10 uM microchannels. Given our preliminary findings, we will investigate the effect of selective GR modulators (SGRMs) on ILC phenotypes and gene expression. We hypothesize that the gene expression changes following GR activation will be different in ILC compared to IDC. In addition, we are examining the genes required for survival of ILC cells on collagen using an in vitro CRISPR-Cas9 screen. In vivo experiments examining the association of GR expression with tumor growth in vivo are ongoing. Citation Format: Ishrat Durdana, Candace Frerich, Muriel Laine, Smita Rindhe, Lynda Bennett, Robert Bachoo, Geoffrey Greene, Suzanne Conzen. Glucocorticoid receptor (GR) activity alters invasive lobular breast cancer (ILC) oncogenic properties. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5283.