Abstract PS5-31: Molecular markers of response to s-equol, a novel oral estrogen receptor (ER) beta agonist for triple negative breast cancer
Authors: Kate Lathrop, Virginia Kaklamani, Andrew Brenner, Rong Li, Alia Nazarullah, Sarah Hackman, Courtney Thomas, Jonathan Gelfond, Marisa Rodriguez, Richard Elledge
Journal: Cancer Research (2021)

Abstract Introduction: Patients with TNBC breast cancer have inferior treatment outcomes compared to other breast cancer subtypes and targeted therapies are lacking. S-equol is a novel oral Estrogen Receptor (ER) Beta agonist with preclinical data showing suppression of TNBC cellular proliferation, and recently presented data showed a decrease in Ki-67 in patients treated with S-equol. This abstract will present the molecular markers that correlate with Ki-67 change in patients with TNBC treated with neoadjuvant S-equol. Methods: We conducted a neoadjuvant window trial that enrolled 39 patients with confirmed TNBC on diagnostic core needle biopsy. Cohort A (20 patients) received a daily dose of 50 mg PO twice daily and Cohort B (19 patients) received a higher dose of 150 mg twice daily. Paired biopsies were evaluable for 36 patients. Both cohorts were treated for a duration of 10-21 days. Primary outcome was change from pre- to post-treatment Ki-67 evaluated by paired t-test and that data was previously published. Secondary endpoints include: Tumor infiltrating lymphocytes in intratumoral and peritumoral (stromal) locations using CD3 (pan T cell) and CD8 (cytotoxic T cell) immunohistochemistry, density of lymphocytes per high power field (40x) for both locations in pre-treatment and post-treatment specimens, Cyclin-D1 protein expression in pre-treatment and post-treatment biopsies as percentage of total tumor cells in pre-treatment and post-treatment specimens, and total estrogen receptor-beta protein expression using immunohistochemistry qualitatively and quantitatively using All-red score in pre-treatment and post-treatment specimens.Results: The primary outcome of Ki-67 decrease of at least 20% from baseline was observed in 28% of the patients. This is a placeholder abstract and an updated abstract with the correlative molecular markers as outlined above will be provided. Conclusion: S-equol is a novel well tolerated oral ER-Beta agonist with inhibition of proliferation in patients with TNBC as measured by a decrease in Ki-67. RNA-seq data, also previously presented, supports potential immune activation during this short period of drug exposure. Future studies aim to evaluate S-equol as an immune activating agent for combination with immunotherapies such as checkpoint inhibitors in TNBC. The pending molecular predictors of response will inform future therapeutic clinical trials for this novel therapy. Citation Format: Kate Lathrop, Virginia Kaklamani, Andrew Brenner, Rong Li, Alia Nazarullah, Sarah Hackman, Courtney Thomas, Jonathan Gelfond, Marisa Rodriguez, Richard Elledge. Molecular markers of response to s-equol, a novel oral estrogen receptor (ER) beta agonist for triple negative breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS5-31.