High eIF4E Overexpression in Node Negative Breast Cancer as Predictor for Recurrence

Abstract

Abstract : The quantity of available eukaryotic Initiation Factor 4E (elF4E) in cells plays a critical role in the regulation of protein synthesis. EIF4E overexpression has been found in human malignancies (Li, 1997; Nathan, 1997). Furthermore, there appears to be an association of eIF4E overexpression and clinical outcomes (Li, 1998; Nathan, 1997; Li, 2001). The purpose of the study is to determine if high eIF4E overexpression %>7-fold increase) in patients with node negative breast cancer is associated with a statistically significant increased risk (2.5-fold) for cancer recurrence when compared to patients with low eIF4E overexpression. The study involves 255 patients treated with definitive local therapy (i.e. breast conservation therapy or modified radical mastectomy) and offered systemic adjuvant therapy per standard of care. The cancer specimens are quantified for elF4E overexpression by Western blot analysis. Each patient undergoes identical clinical surveillance. Initial clinical stage, elF4E overexpression, and clinical outcomes data are coded and researchers are blinded until data analysis at the end of the study. The primary endpoint measured is breast cancer recurrence; local, regional and/or distant. The projected study accrual time is 3 years, with targeted study completion in 5 years. To date 142 patients have been accrued, 133 patients have cancer specimens quantified for eIF4E level. In an interim analysis of 111 patients, in patients with the highest tertile of elF4E level (>14-fold), the relative risk for cancer recurrence was 6.2 x that of the low eIF4E group (<7-fold) (p=O.O26).