Royal College of Surgeons in Ireland
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Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer

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journal contribution
posted on 2022-12-01, 16:10 authored by Funda Meric-Bernstam, Huiqin Chen, Argun Akcakanat, Kim-Anh Do, Ana Lluch, Bryan HennessyBryan Hennessy, Gabriel N Hortobagyi, Gordon B Mills, Ana Gonzalez-Angulo

Introduction: Translation initiation is activated in cancer through increase in eukaryotic initiation factor 4E (eIF4E), eIF4G, phosphorylated eIF4E-binding protein (p4E-BP1) and phosphorylated ribosomal protein S6 (pS6), and decreased programmed cell death protein 4 (pdcd4), a translational inhibitor. Further, translation elongation is deregulated though alterations in eukaryotic elongation factor 2 (eEF2) and eEF2 kinase (eEF2K). We sought to determine the association of these translational aberrations with clinical-pathologic factors and survival outcomes in hormone receptor-positive breast cancer.

Methods: Primary tumors were collected from 190 patients with Stage I to III hormone receptor-positive breast cancer. Expression of eIF4E, eIF4G, 4E-BP1, p4E-BP1 T37/46, p4E-BP1 S65, p4E-BP1 T70, S6, pS6 S235/236, pS6 S240/244, pdcd4, eEF2 and eEF2K was assessed by reverse phase protein arrays. Univariable and multivariable analyses for recurrence-free survival (RFS) and overall survival (OS) were performed.

Results: High eEF2, S6, pS6 S240/244, p4E-BP1 T70, and low pdcd4 were significantly associated with node positivity. Median follow-up for living patients was 96 months.

Conclusions: Increased pS6, p4E-BP1, eEF2K and decreased pdcd4 are associated with poor prognosis in hormone receptor-positive breast cancer, suggesting their role as prognostic markers and therapeutic targets.


Susan G. Komen for the Cure Grant SAC10006

Stand Up to Cancer Dream Team Translational Research Grant, a program of the Entertainment Industry Foundation (SU2CAACR-DT0209)

Society of Surgical Oncology Clinical Investigator Award in Breast Cancer Research

Kleberg Center for Molecular Markers at the University of Texas MD Anderson Cancer Center

Susan G. Komen Foundation FAS0703849

Cancer Center Support Grant CCSG P30 CA016672

National Center for Research Resources Grant 3UL1RR024148

National Center for Advancing Translational Sciences Grant UL1TR000371



The original article is available at

Published Citation

Meric-Bernstam F. et al. Aberrations in translational regulation are associated with poor prognosis in hormone receptor-positive breast cancer. Breast Cancer Res. 2012;14(5):R138.

Publication Date

26 October 2012

PubMed ID



  • Beaumont Hospital
  • Medicine


BioMed Central


  • Published Version (Version of Record)