Prnewswire·2025-12-15 13:00Core Insights - Atossa Therapeutics presented four clinical trial updates on (Z)-endoxifen at the San Antonio Breast Cancer Symposium, highlighting its potential in breast cancer treatment and risk reduction [1][2] Clinical Trial Updates - The company emphasized the therapeutic value of (Z)-endoxifen across the breast care continuum, with ongoing enrollment in the Phase 2 EVANGELINE study for neoadjuvant ER+/HER2- breast cancer [2] - Initial results from the RECAST trial suggest that short-term endocrine therapy combined with MRI response assessment may help identify low-risk DCIS patients who can avoid surgery [3][7] - Low-dose (Z)-endoxifen demonstrated excellent tolerability and biological activity, with significant reductions in Ki-67 (–72% median), MRI tumor volume, and ctDNA clearance in 70% of initially ctDNA-positive patients [5][8] - The EVANGELINE trial is the first to evaluate (Z)-endoxifen with ovarian function suppression as a neoadjuvant therapy for premenopausal ER+/HER2- breast cancer, showing strong early biological activity with 86% of patients achieving a Week 4 Ki-67 of 10% [10][15] Mechanistic Insights - (Z)-endoxifen maintains potent ER antagonist activity against key ESR1 mutations, stabilizing inactive receptor conformations and demonstrating strong suppression of ER signaling [6][14] - Transcriptomic analyses indicate that (Z)-endoxifen reverses multiple mutant ESR1-associated oncogenic pathways while restoring beneficial programs, highlighting its therapeutic potential for ER+/ESR1 mutant breast cancer [14]