title: Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients.
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.
authors.affiliation: Department of Obstetrics and Gynecology, Diakonischen Dienste Hannover GmbH, Diakoniekrankenhaus Henriettenstiftung und Diakoniekrankenhaus Friederikenstift, Hanover, Germany.
authors.forename: Wulf
authors.initials: W
authors.lastname: Siggelkow
authors.forename: Daniel
authors.initials: D
authors.lastname: Boehm
authors.forename: Susanne
authors.initials: S
authors.lastname: Gebhard
authors.forename: Marco
authors.initials: M
authors.lastname: Battista
authors.forename: Isabel
authors.initials: I
authors.lastname: Sicking
authors.forename: Antje
authors.initials: A
authors.lastname: Lebrecht
authors.forename: Christine
authors.initials: C
authors.lastname: Solbach
authors.forename: Birte
authors.initials: B
authors.lastname: Hellwig
authors.forename: Jörg
authors.initials: J
authors.lastname: Rahnenführer
authors.forename: Heinz
authors.initials: H
authors.lastname: Koelbl
authors.forename: Mathias
authors.initials: M
authors.lastname: Gehrmann
authors.forename: Rosemarie
authors.initials: R
authors.lastname: Marchan
authors.forename: Cristina
authors.initials: C
authors.lastname: Cadenas
authors.forename: Jan G
authors.initials: JG
authors.lastname: Hengstler
authors.forename: Marcus
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D064096:Aurora Kinase A; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D011960:Receptors, Estrogen / Q000235:genetics; D059467:Transcriptome
chemical_list: D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human; C576917:AURKA protein, human