A prospective trial on initiation factor 4E (eIF4E) overexpression and cancer recurrence in node-negative breast cancer.
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.
Holm
Neal
N
Louisiana State University Health Sciences Center and Feist-Weiller Cancer Center, 1501 Kings Highway, Shreveport, LA 71130, USA.
Byrnes
Kerry
K
Johnson
Lester
L
Abreo
Fleurette
F
Sehon
Kenneth
K
Alley
JoAnn
J
Meschonat
Carol
C
Md
Quyen Chu
QC
Li
Benjamin D L
BD
D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D015410:Mastectomy, Extended Radical; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D009367:Neoplasm Staging; D011446:Prospective Studies; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D039561:Eukaryotic Initiation Factor-4E