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Breast Cancer Research
Published in: Breast Cancer Research 3/2007

Open Access 01-06-2007 | Research article

Low E2F1 transcript levels are a strong determinant of favorable breast cancer outcome

Authors: Vincent Vuaroqueaux, Patrick Urban, Martin Labuhn, Mauro Delorenzi, Pratyaksha Wirapati, Christopher C Benz, Renata Flury, Holger Dieterich, Frédérique Spyratos, Urs Eppenberger, Serenella Eppenberger-Castori

Published in: Breast Cancer Research | Issue 3/2007

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Abstract

Introduction

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.

Conclusion

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.
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Metadata
Title
Low E2F1 transcript levels are a strong determinant of favorable breast cancer outcome
Authors
Vincent Vuaroqueaux
Patrick Urban
Martin Labuhn
Mauro Delorenzi
Pratyaksha Wirapati
Christopher C Benz
Renata Flury
Holger Dieterich
Frédérique Spyratos
Urs Eppenberger
Serenella Eppenberger-Castori
Publication date
01-06-2007
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2007
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr1681

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