Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients
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
Citation and License
BMC Cancer 2012, 12:562 doi:10.1186/1471-2407-12-562Published: 27 November 2012
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).
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.
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).
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.