26. Initiation Factor 4E (eIF4E) and Cancer Recurrence In Node-Positive Breast Carcinoma
Benjamin D. Li, MD*1, Derek McClusky, MD*1, Richard H. Turnage, MD1, John C. McDonald, MD1, Herbert Yu, MD, PhD*2, Quyen Chu, MD*1, Lester W. Johnson, MD*1, Arrigo DeBenedetti, PhD*1
1Louisiana State University, Shreveport, LA; 2Yale University, New Haven, CT
Objective: Previous study of stage I to III breast cancer patients showed that those with the highest tertile eIF4E overexpression had a higher risk for recurrence. This study is designed to determine if high eIF4E overexpression predicts cancer recurrence independent of nodal status by specifically studying node-positive (node+) patients.
Methods: The trial design was to accrue 168 node+ patients to detect a 2.5-fold increase in risk for recurrence. eIF4E level was quantified by Western blots as x-fold elevated relative to breast tissue from non-cancer patients. Endpoints measured were disease recurrence and cancer-related death. Statistical analyses performed include Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model.
Results: 174 patients were accrued prospectively. They fulfilled study inclusion and exclusion criteria, treatment protocol, and surveillance requirements. Mean eIF4E elevation was 11.0+7.0-fold (mean+s.d.). Based on previously published tertile determination, patients were grouped: 1) lowest tertile (<7.5-fold)=67 patients, 2) intermediate tertile (7.5 to 14-fold)=54 patients 3) highest tertile (>14-fold)=53 patients. At a median follow-up of 32 months, the highest tertile group had a statistically significant higher cancer recurrence (p=0.002, log rank test) and cancer-related death (p=0.036) than the lowest tertile group. Highest tertile patients had a 2.4-fold relative risk increase for recurrence (95% C.I.=1.2-4.7, p=0.015).
Conclusions: In this prospective trial designed specifically to address risk for recurrence in node+ patients, the highest tertile eIF4E overexpression resulted in a 2.4-fold relative risk increase for cancer recurrence. This supports our hypothesis that high eIF4E overexpression is a predictor of cancer recurrence independent of nodal status.