Abstract
BackgroundInhibitors 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).MethodsAURKA 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.ResultsPatients 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).ConclusionsAURKA 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.
Highlights
Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed
AURKA was associated with metastasis-free interval (MFI) in the Hormone receptor status1
Progesterone receptor and HER-2 status were derived from the gene array data
Summary
Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Aurora kinases A and B are both important for cell cycle progression They are frequently overexpressed or mutated in human tumor proteins [1,2], and have been implicated in tumor formation and progression [3,4]. Polymorphisms in the AURKA gene are associated with increased risk of primary breast cancer [10,11]. Other studies have assessed the expression of AURKA in human breast cancer tissue. A larger study including 112 patients did not find an association between AURKA expression and survival [16]. Aurora kinase B expression was not associated with survival [17]
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