A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-negative breast cancer

Ann Surg Oncol. 2008 Nov;15(11):3207-15. doi: 10.1245/s10434-008-0086-9. Epub 2008 Aug 22.


Background: Eukaryotic Initiation Factor 4E (eIF4E) plays a crucial role in translation control. High eIF4E increase in tumor specimens independently predicted recurrence by multivariate analysis. This prospective trial of node-negative only breast cancer patients was initiated to test the hypothesis that high eIF4E increase predicts cancer recurrence and death, independent of nodal status.

Methods: The trial was powered to detect a 2.4-fold increase in relative risk for cancer recurrence in 240 node-negative patients on the basis of high versus low eIF4E increase in tumor specimens (type I error = .05, statistical power = .08). eIF4E level was quantified by using Western blot test. Treatment and surveillance regimens were standardized. Primary endpoints were cancer recurrence and cancer-related death.

Results: Of the 242 patients accrued, 112 were in the low eIF4E group (<7.5-fold), 82 were in the intermediate eIF4E group (7.5- to 15-fold), and 48 were in the high eIF4E group (>15-fold). Patients in the high eIF4E group had a statistically significant higher rate of cancer recurrence and cancer-related death (P = .0001 and P < or = .0001, log rank test). The relative risk for cancer recurrence was 2.2-fold higher in the high eIF4E group (P = .001, Cox model), and 3.7-fold higher for cancer-related death (P = .0009).

Conclusions: In node-negative breast cancer, high eIF4E increase predicted a higher rate of cancer recurrence and death. High eIF4E patients had a >2-fold increase in relative risk for cancer recurrence and nearly a 4-fold increase in relative risk for death. This supports our hypothesis that high eIF4E is an independent predictor for breast cancer outcome independent of nodal status.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Ductal, Breast / surgery
  • Eukaryotic Initiation Factor-4E / metabolism*
  • Female
  • Humans
  • Lymph Nodes / metabolism*
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Mastectomy, Extended Radical
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Prospective Studies
  • Risk Factors
  • Survival Rate


  • Biomarkers, Tumor
  • Eukaryotic Initiation Factor-4E