Eukaryotic translation initiation factor 4E (eIF4E) expression is associated with breast cancer tumor phenotype and predicts survival after anthracycline chemotherapy treatment

Breast Cancer Res Treat. 2013 Aug;141(1):79-88. doi: 10.1007/s10549-013-2671-2. Epub 2013 Aug 24.

Abstract

Abnormal translation of mRNAs frequently occurring during carcinogenesis is among the mechanisms that can affect the expression of proteins involved in tumor development and progression. Eukaryotic initiation factor eIF4E is a key regulator of translation of many cancer-related transcripts and its expression is altered in various cancers and has been associated with worse survival. We determined the eIF4E protein levels using immunohistochemistry (IHC) in 1,233 breast tumors on tissue microarrays. We analyzed the effects of the IHC expression level on tumor characteristics and patient survival, also with stratification by adjuvant chemotherapy treatment. In 1,085 successfully stained tumors, high level of eIF4E protein expression was associated with features of aggressive tumor phenotype, namely grade, estrogen and progesterone receptor negativity, HER2 receptor positivity, and high expression of p53 and Ki67, and with triple negative subtype (p < 0.001). High eIF4E expression was associated with worse breast cancer-specific survival with a hazard ratio (HR) of 1.99 (95 % CI 1.32-3.00, p = 0.0008) and was in a multivariate analysis an independent prognostic factor. High eIF4E expression was associated with worse outcome also after detection of distant metastasis (HR = 1.88, 95 % CI 1.20-2.94, p = 0.0060). In the subgroup analysis the survival effect was strongest among patients treated with anthracycline chemotherapy (HR = 3.34, 95 % CI 1.72-6.48, p = 0.0002), whereas no such effect was seen among patients who had not received anthracycline with significant difference in heterogeneity between the two groups (p = 0.0358). High expression of eIF4E is associated with adverse tumor characteristics and predicts poor breast cancer-specific survival. This effect is emphasized in patients treated with anthracycline chemotherapy. eIF4E as a treatment predictive factor warrants further studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / analysis
  • Breast Neoplasms / chemistry*
  • Breast Neoplasms / classification
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Carcinoma / chemistry*
  • Carcinoma / classification
  • Carcinoma / drug therapy
  • Carcinoma / mortality
  • Carcinoma / pathology
  • Carcinoma / therapy
  • Chemotherapy, Adjuvant
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Doxorubicin / administration & dosage
  • Epirubicin / administration & dosage
  • Eukaryotic Initiation Factor-4E / analysis*
  • Eukaryotic Initiation Factor-4E / biosynthesis
  • Eukaryotic Initiation Factor-4E / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kaplan-Meier Estimate
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Proteins / analysis*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Paraffin Embedding
  • Phenotype
  • Prognosis
  • Protein Biosynthesis
  • Tissue Array Analysis
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / chemistry
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • Eukaryotic Initiation Factor-4E
  • Neoplasm Proteins
  • Cytarabine
  • Epirubicin
  • Doxorubicin
  • Cyclophosphamide

Supplementary concepts

  • CEF regimen