Abstract 3616: Potential therapeutic use of Estrogen Receptor β agonist in the prevention and progression of breast cancer using HER-2/neu mouse model

Abstract

Abstract Breast cancer is the most common cancer among women worldwide. Hormone-mediated therapy to treat estrogen receptor alpha (ERα) positive breast cancers include the use of ER antagonist, Tamoxifen, aromatase inhibitors and other compounds that degrade ERα. Unlike ERα, ERβ has been shown to have tumor-suppressive function in various cancers, including breast cancer. Recent studies have identified, synthesized, and tested the clinical safety of ERβ-selective agonists. Given the tumor-suppressive properties of ERβ, it may be possible to use these compounds to induce or activate the ERβ and test their role in the chemoprevention and blocking the progression of breast cancer. We have investigated the therapeutic utility of ERβ agonists in the prevention and progression of breast cancer using MMTV-HER2/neu mice transgenic mouse model. MMTV-HER2/neu mice develop premalignant lesions at 4-5 months, and tumors starting at month 7 due to overexpression of the HER2/neu proto-oncogene. MMTV-HER2/neu mice were treated with an ERβ agonist, LY500307 examined the prevention and progression of mammary cancers in these mice. When compared to controls, ERβ agonist-treated mice exhibited a significant decrease in the development of preneoplastic changes. Differential gene expression analysis revealed a significant change in the expression of a number of genes in response to LY500307 treatment. Pathway analysis identified an enrichment for chemokines signaling pathways, particularly TNF, in blocking the development of preneoplastic changes resulting from treatment with ERβ agonists. Our studies also show a decrease in the formation of mammary tumors in HER-2/neu mice with preexisting preneoplastic changes when treated with LY500307. This study suggests that ERβ agonist treatment may be a valuable therapeutic option for the prevention in women at increased risk of breast cancer and in blocking the progression of hormone receptor positive breast tumors. Citation Format: Kumaraguruparan Ramasamy, Cathy Samayoa, Naveen K. Krishnegowda, Ratna K. Vadlamudi, Rajeshwar R. Tekmal. Potential therapeutic use of Estrogen Receptor β agonist in the prevention and progression of breast cancer using HER-2/neu mouse model [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3616. doi:10.1158/1538-7445.AM2017-3616