Abstract 5550: Crosstalk of estrogen receptor Β with tumor microenvironment signaling explains tumor suppressor actions in TNBC

Abstract Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer lacking molecular targets, possessing one of the poorest prognoses of all breast cancers. Recent studies using breast tumor samples show an association between the expression of estrogen receptor β (ERβ) and improved survival of patients with TNBC. ERβ - whose function largely opposes that of oncogenic ERα - is involved in the regulation of many tumor repressive pathways and has lately been observed to partake in immune modulation, thus presenting a promising target for TNBC. Discovering selective ERβ agonists is critical to understanding the potential of activating the receptor as a therapy approach for TNBC. It enables us to elicit estrogen signaling response specific to the tumor suppressive function of the β receptor subtype. We have set out a screening process to test and identify ligands that display the greatest activation and specificity for ERβ as determined by reporter assays and changes in downstream target gene expression. We selected to study in vitro and in vivo the compounds with optimal biological activity to delineate tumor-intrinsic and -extrinsic effects and validate the mechanism of action employing human and mouse cell models that reflect the heterogeneity of the disease. We propose that activation of ERβ decreases the proliferative and metastatic ability of breast cancer cells by altering cellular pathways and crosstalk with immune cells. The results of these studies help lay the groundwork for further research on the clinical potential of ERβ especially in the realm of immunotherapy and treatment of TNBC. Citation Format: Kristina Diana A. Zambo, Harika Nagandla, Kim Cuong Cap, Aireana Phillips, Fotis Nikolos, Wei Qian, Jianying Zhou, Jenny Chang, Christoforos Thomas. Crosstalk of estrogen receptor Β with tumor microenvironment signaling explains tumor suppressor actions in TNBC abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 5550.