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Open Access Research article

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

Wulf Siggelkow1, Daniel Boehm2, Susanne Gebhard2, Marco Battista2, Isabel Sicking2, Antje Lebrecht2, Christine Solbach2, Birte Hellwig3, Jörg Rahnenführer3, Heinz Koelbl2, Mathias Gehrmann4, Rosemarie Marchan5, Cristina Cadenas5, Jan G Hengstler5 and Marcus Schmidt26*

Author affiliations

1 Department of Obstetrics and Gynecology, Diakonischen Dienste Hannover GmbH, Diakoniekrankenhaus Henriettenstiftung und Diakoniekrankenhaus Friederikenstift, Hanover, Germany

2 Department of Obstetrics and Gynecology, Johannes Gutenberg University, Mainz, Germany

3 Department of Statistics, Dortmund TU, Dortmund, Germany

4 Bayer GmbH, Leverkusen, Germany

5 IfADo-Leibniz Research Centre for Working Environment and Human Factors (IfADo), Technical University of Dortmund, Dortmund, Germany

6 Department of Obstetrics and Gynecology, University of Mainz, Langenbeckstr. 1, Mainz, 55131, Germany

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Citation and License

BMC Cancer 2012, 12:562  doi:10.1186/1471-2407-12-562

Published: 27 November 2012

Abstract

Background

Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766).

Methods

AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered.

Results

Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45– 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14–2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70–2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24–2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001).

Conclusions

AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.

Keywords:
Aurora kinase; Node-negative breast cancer; Breast cancer; Prognosis; Aurora kinase inhibitors