Abstract 2017: Eukaryotic translation initiator factor 4E in breast cancer progression and prognosis

Abstract The network of the eukaryotic translation initiator factor 4E (eIF4E), a mRNA cap-binding protein that is critical in the translation initiation of protein synthesis and the downstream effector of PI3K/AKT/mTOR and RTK/RAS/ERK signaling pathways, is implicated in tumorigenesis and tumor progression through regulation of cell proliferation, angiogenesis and metastasis. Targeting eIF4E with e.g. eIF4E/cap interaction antagonists, siRNA and antisense oligonucleotides is in preclinical and early clinical development and may evolve as one of the effective cancer treatments. However, there has been a dearth of data of eIF4E translational research for tumor progression clinically and prognosis. In this study, we investigated the expression of eIF4E by immunohistochemistry, and its association with clinicopathological factors and prognosis in a cohort of 710 cases of nonmetastatic breast cancer. eIF4E was expressed in 50% formalin-fixed and paraffin-embedded primary invasive breast cancer. The cap-binding protein in high-grade tumors was more prominent in the eIF4E-positive tumors than eIF4E-negative tumors (p=0.0005). Its expression was associated with larger tumor size (p=0.0001) and node-positive disease (p=0.006). In addition, there was more estrogen receptor/progesterone receptor negativity in eIF4E-positive than eIF4E-negative tumors. Notably, eIF4E demonstrated a significance towards association with both overall survival and recurrence-free survival (p=0.04 and p=0.03 by Gehan-Breslow-Wilcoxon test). The significance in the survival and recurrence outcomes was evident within 10 years of follow-up and the difference gradually diminished with long-term follow-up after 10 years. Taken together, eIF4E is linked to clinical tumor progression through its association with larger tumor size and nodal involvement as well as with high tumor grade. It has a role for prognosis in patients who were diagnosed with nonmetastatic breast cancer particularly within 10 years of clinical follow-up. Citation Format: Dat Nguyen, Angelo Laranjeira, John Yu, Stephen M. Hewitt, Sherry X. Yang. Eukaryotic translation initiator factor 4E in breast cancer progression and prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 2017.