Abstract 3231: Chromatin profiling reveals the impact of fulvestrant on estrogen receptor-driven chromatin dynamics in breast cancer cells

Abstract Background: Epigenetic dysregulations are linked to various diseases, including cancer. Among them, breast cancer is the second leading cause of cancer-related deaths in women with 50% of mortalities attributable to estrogen receptor-positive (ER+) tumors. Endocrine therapies targeting the ER such as Tamoxifen, Fulvestrant (FULV) and Aromatase inhibitors, are widely used in the clinic. Among these therapeutic agents, FULV has been shown to fully antagonize ER activity, primarily through the rapid degradation and elimination of ER from target tissues. However, recent findings indicate that ER, when engaged with FULV, retains the ability to translocate to the nucleus and bind DNA whereas appearing transcriptionally inert. Results: In this study, we aimed to further investigate the effects of FULV and Estradiol (E2), the natural ER ligand, on ER cistrome, chromatin accessibility, gene transcription, and H3K27ac genome-wide patterns in ER+ breast cancer cell lines. Using the innovative CUT Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 3231.