Overexpression of eukaryotic initiation factor 4E is correlated with increased risk for systemic dissemination in node-positive breast cancer patients.

Abstract

BACKGROUND:

Molecular events impact systemic dissemination. Overexpression of eukaryotic initiation factor 4E (eIF4E) has been shown to predict worse clinical outcomes in breast cancer. Node-positive breast cancer patients were specifically studied to determine if eIF4E elevation increases risk for systemic dissemination.

STUDY DESIGN:

Two hundred two node-positive breast cancer patients were prospectively accrued and treated with standardized treatment and surveillance protocol. Tumor eIF4E protein level was quantified by Western blots as x-fold over benign samples from noncancer patients. Primary end point was systemic metastasis.

RESULTS:

Systemic recurrence was detected in 22.2% of the low eIF4E group, 27.3% of the intermediate group, and 49% of the high group, at a median follow-up of 47 months. A greater risk for systemic metastasis was seen in the high eIF4E group compared with the low group (log-rank test, p = 0.0084). Patients in the high eIF4E group had a 1.5-fold (hazard ratio = 1.52; 95% CI, 1.07-2.17; p = 0.0206) higher risk for systemic metastasis than the low group. Sixty percent of the patients with high eIF4E were observed to have metastasis to multiple sites, compared with 50% in the intermediate group, and 14.5% in the low group (p = 0.02, Fisher's exact test). When patients were segregated based on nodal classification (N1, N2, and N3), eIF4E overexpression continued to be a predictor for systemic dissemination in patients with N1 disease.

CONCLUSIONS:

High eIF4E is correlated with an increased risk for systemic metastasis in node-positive breast cancer patients. High eIF4E overexpression was associated with a higher incidence of metastasis to multiple sites. Therefore, high eIF4E overexpression appears to be a marker for molecular events that increases risk for systemic dissemination.

• Authors: Xuedong Yin, Roger H Kim, Guang Sun, Janet K Miller, Benjamin D Li
• Journal: Journal of the American College of Surgeons (J Am Coll Surg) Vol. 218 Issue 4 Pg. 663-71 (Apr 2014) ISSN: 1879-1190 [Electronic] United States
• PMID: 24491247 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Eukaryotic Initiation Factor-4E

Topics

• Biomarkers, Tumor (metabolism)
• Blotting, Western
• Breast Neoplasms (metabolism, mortality, pathology, therapy)
• Combined Modality Therapy
• Eukaryotic Initiation Factor-4E (metabolism)
• Female
• Follow-Up Studies
• Humans
• Lymphatic Metastasis
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Prospective Studies
• Risk
• Survival Analysis