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Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer

Oncogene volume 22, pages 4898–4904 (2003)Cite this article

Abstract

Recently, cyclin-E was reported to be the most prominent prognostic factor for breast cancer outcome described so far, even surpassing axillary nodal involvement. Earlier studies on the prognostic value of cyclin-E in breast cancer, however, yielded heterogeneous results. Therefore, we set out to confirm and extend these results by quantitative Taqman RT–PCR of cyclin-E levels in 277 resectable breast cancers. Cyclin-E levels were not associated with relapse-free survival (RFS) or overall survival (OS) in the total cohort of patients, or in the subset of patients without involved lymph nodes that were not treated with adjuvant systemic therapy. Besides several classical clinicopathological factors, the interaction between cyclin-E and adjuvant endocrine therapy (P=0.01, HR=3.04, 95% CI: 1.30–7.09) was found to contribute significantly in multivariate analyses. Cyclin-E levels were associated with poor RFS specifically in patients treated with adjuvant endocrine therapy (n=108, P=0.001, HR=4.01, 95% CI: 1.76–9.12), independent of estrogen receptor status. In conclusion, cyclin-E is not a pure prognostic factor in breast cancer, but rather a predictor of failure of endocrine therapy. Differences in literature on the presumed prognostic value of cyclin-E may be due to differences in treatment. Assessment of cyclin-E levels can aid in improving adjuvant treatment selection.

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Acknowledgements

We thank the contributors, especially the surgeons and internists, of the University Medical Center Nijmegen, Nijmegen; Ziekenhuis Apeldoorn, Apeldoorn; Deventer Ziekenhuis, Deventer; Nieuw Spitaal, Zutphen; and Streekziekenhuis Zevenaar, Zevenaar, The Netherlands, for their assistance in collecting the patients' clinical follow-up data. Doorlène van Tienoven and Anneke Geurts-Moespot are acknowledged for their work with collecting and archiving the breast tumor samples. Joop Heuvel is greatly acknowledged for his expert technical assistance.

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Authors and Affiliations

  1. Department of Chemical Endocrinology, University Medical Center Nijmegen, Nijmegen, The Netherlands

    Paul N Span, Peggy Manders & C G J (Fred) Sweep

  2. Department of Medical Oncology, University Medical Center Nijmegen, Nijmegen, The Netherlands

    Vivianne C G Tjan-Heijnen, Peggy Manders & Louk V A M Beex

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  1. Paul N Span
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  2. Vivianne C G Tjan-Heijnen
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  3. Peggy Manders
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Correspondence to Paul N Span.

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Span, P., Tjan-Heijnen, V., Manders, P. et al. Cyclin-E is a strong predictor of endocrine therapy failure in human breast cancer. Oncogene 22, 4898–4904 (2003). https://doi.org/10.1038/sj.onc.1206818

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