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. 2007;9(3):R33.
doi: 10.1186/bcr1681.

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

Vincent Vuaroqueaux  1 , Patrick Urban, Martin Labuhn, Mauro Delorenzi, Pratyaksha Wirapati, Christopher C Benz, Renata Flury, Holger Dieterich, Frédérique Spyratos, Urs Eppenberger, Serenella Eppenberger-Castori
Affiliations

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

Vincent Vuaroqueaux et al. Breast Cancer Res. 2007.

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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Figures

Figure 1
Figure 1
Estrogen receptor and ERBB2 versus E2F1 expression levels. Scatter plots of estrogen receptor (ER) ESR1 and ERBB2 versus E2F1 expression levels in (a), (b) the Stiftung Tumorbank Basel data (STB) set and (c), (d) The Netherlands Cancer Institute (NKI) data set. Open circles, no metastasis; filled circles, metastasis. Vertical lines, cutoff values for the estrogen receptor (ER) and ERBB2 status, respectively; horizontal lines, 30th percentile for E2F1. Combined Kaplan–Meier analysis (metastasis-free survival) using the ER or ERBB2 status and E2F1 (30th percentile) in (e), (f) the STB data set and (g), (h) the NKI data set. Labels of the survival curves correspond to the groups as indicated on the respective scatter plot. CI, 95% confidence interval; HR, hazard ratio.
Figure 2
Figure 2
Comparison of E2F1 and the 70-gene signature in The Netherlands Cancer Institute data set. (a), (b) Scatter plots of estrogen receptor (ER = ESR1) and ERBB2 versus E2F1 expression levels. Open circles, poor-prognosis group as defined by [5]; filled circles, good-prognosis group [5]. (c) Correlation between the 70-gene prognostic signature and E2F1. Open circles, no metastasis; filled circles, metastasis.
Figure 3
Figure 3
Kaplan–Meier analysis of metastasis-free survival. Kaplan–Meier analysis (metastasis-free survival) using (a) E2F1 expression (30th percentile) and the 70-gene signature, (B) intrinsic subtypes, (c) the recurrence score (Rsu), and (b) the wound response signature. CI, 95% confidence interval; HR, hazard ratio.
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