Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients
Menée sur trois cohortes indépendantes comportant au total 766 patientes atteintes d'un cancer du sein sans invasion ganglionnaire et n'ayant pas reçu de traitement systémique adjuvant, cette étude montre une association entre l'expression de la kinase aurora A et la survie sans métastase
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.
BMC Cancer , article en libre accès, 2011