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


METHODS
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.
Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA; Department of Endocrine Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
Xuedong
X
Yin
Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA.
Roger H
RH
Kim
Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA.
Guang
G
Sun
Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA.
Janet K
JK
Miller
Department of Surgery, Louisiana State University Health Sciences Center, Feist-Weiller Cancer Center, Shreveport, LA. Electronic address: bli@lsuhsc.edu.
Benjamin D
BD
Li
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D003131:Combined Modality Therapy; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011446:Prospective Studies; D012306:Risk; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D039561:Eukaryotic Initiation Factor-4E