Low E2F1 transcript levels are a strong determinant of favorable breast cancer outcome.
BACKGROUND
We investigated whether mRNA levels of E2F1, a key transcription factor involved in proliferation, differentiation and apoptosis, could be used as a surrogate marker for the determination of breast cancer outcome.


METHODS
E2F1 and other proliferation markers were measured by quantitative RT-PCR in 317 primary breast cancer patients from the Stiftung Tumorbank Basel. Correlations to one another as well as to the estrogen receptor and ERBB2 status and clinical outcome were investigated. Results were validated and further compared with expression-based prognostic profiles using The Netherlands Cancer Institute microarray data set reported by Fan and colleagues.


RESULTS
E2F1 mRNA expression levels correlated strongly with the expression of other proliferation markers, and low values were mainly found in estrogen receptor-positive and ERBB2-negative phenotypes. Patients with low E2F1-expressing tumors were associated with favorable outcome (hazard ratio = 4.3 (95% confidence interval = 1.8-9.9), P = 0.001). These results were consistent in univariate and multivariate Cox analyses, and were successfully validated in The Netherlands Cancer Institute data set. Furthermore, E2F1 expression levels correlated well with the 70-gene signature displaying the ability of selecting a common subset of patients at good prognosis. Breast cancer patients' outcome was comparably predictable by E2F1 levels, by the 70-gene signature, by the intrinsic subtype gene classification, by the wound response signature and by the recurrence score.


CONCLUSIONS
Assessment of E2F1 at the mRNA level in primary breast cancer is a strong determinant of breast cancer patient outcome. E2F1 expression identified patients at low risk of metastasis irrespective of the estrogen receptor and ERBB2 status, and demonstrated similar prognostic performance to different gene expression-based predictors.
Vuaroqueaux
Vincent
V
Stiftung Tumorbank Basel, Lörracherstrasse 50, 4125 Riehen, Switzerland. v.vuaroqueaux@tumorbank.org
Urban
Patrick
P
Labuhn
Martin
M
Delorenzi
Mauro
M
Wirapati
Pratyaksha
P
Benz
Christopher C
CC
Flury
Renata
R
Dieterich
Holger
H
Spyratos
Frédérique
F
Eppenberger
Urs
U
Eppenberger-Castori
Serenella
S
D000328:Adult; D000368:Aged; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002454:Cell Differentiation; D002455:Cell Division; D003131:Combined Modality Therapy; D050687:E2F1 Transcription Factor / Q000235:genetics*; D005260:Female; D006801:Humans; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D016896:Treatment Outcome
D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D012333:RNA, Messenger; D011960:Receptors, Estrogen