Abstract ES9-3: Androgen, progesterone and glucocorticoid receptors: Drivers of breast tumor progression or reprogramming of steroid receptors during breast tumor progression

Abstract

Abstract In normal physiology, glucocorticoid receptor (GR) activity regulates thousand of genes whose products modulate metabolism, inflammation, cell cycle and apoptosis/cell survival pathways. Synthetic GR agonists, or glucocorticoids (GCs), are often used to treat hematologic malignancies because of GR's ability to induce proapoptotic gene expression, inhibit nuclear factor – κB, and induce cell cycle arrest. In contrast, recent examination of GR expression and activity in human breast cancer models and clinical specimens has suggested that GR expression has remarkably diverse roles in breast cancer subtypes. In ER+ breast cancer, GR appears to modulate ER-regulated transcriptional activity through ER/GR receptor crosstalk resulting in antagonism of ER-associated proliferation. However, in ER-negative breast cancer (including TNBC), high tumor GR expression is associated with poor prognosis, anti-apoptotic signaling, and chemotherapy resistance. In addition, high GR activity in the tumor microenvironment is predicted to be immunosuppressive. Recently described selective GR modulators are expected to help dissect divergent GR mechanisms present in breast cancer subtypes. Citation Format: Conzen SD. Androgen, progesterone and glucocorticoid receptors: Drivers of breast tumor progression or reprogramming of steroid receptors during breast tumor progression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES9-3.