Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers

Margret Aradottir; Sigridur T Reynisdottir; Olafur A Stefansson; Jon G Jonasson; Asgerdur Sverrisdottir; Laufey Tryggvadottir; Jorunn E Eyfjord; Sigridur K Bodvarsdottir

doi:10.1002/cjp2.6

Aurora A is a prognostic marker for breast cancer arising in BRCA2 mutation carriers

J Pathol Clin Res. 2014 Nov 7;1(1):33-40. doi: 10.1002/cjp2.6. eCollection 2015 Jan.

Authors

Margret Aradottir¹, Sigridur T Reynisdottir¹, Olafur A Stefansson¹, Jon G Jonasson², Asgerdur Sverrisdottir³, Laufey Tryggvadottir⁴, Jorunn E Eyfjord¹, Sigridur K Bodvarsdottir¹

Affiliations

¹ Cancer Research Laboratory, Biomedical Center, Faculty of Medicine, School of Health Sciences, University of Iceland Reykjavik Iceland.
² Faculty of MedicineSchool of Health Sciences, University of IcelandReykjavikIceland; Icelandic Cancer RegistryIcelandic Cancer SocietyReykjavikIceland; Department of PathologyNational University HospitalReykjavikIceland.
³ Department of Medical Oncology National University Hospital Reykjavik Iceland.
⁴ Faculty of MedicineSchool of Health Sciences, University of IcelandReykjavikIceland; Icelandic Cancer RegistryIcelandic Cancer SocietyReykjavikIceland.

PMID: 27499891
PMCID: PMC4858119
DOI: 10.1002/cjp2.6

Abstract

Overexpression of the Aurora A kinase has been shown to have prognostic value in breast cancer. Previously, we showed a significant association between AURKA gene amplification and BRCA2 mutation in breast cancer. The aim of this study was to assess the prognostic impact of Aurora A overexpression on breast cancer arising in BRCA2 mutation carriers. Aurora A expression was evaluated by immunohistochemistry on breast tumour tissue microarrays from 107 BRCA2 999del5 mutation carriers and 284 of sporadic origin. Prognostic value of Aurora A nuclear staining was estimated in relation to clinical markers and adjuvant treatment, using multivariate Cox's proportional hazards ratio regression model. BRCA2 wild-type allele loss was measured by TaqMan in BRCA2 mutated tumour samples. All statistical tests were two sided. Multivariate analysis of breast cancer-specific survival, including proliferative markers and treatment, indicated independent prognostic value of Aurora A nuclear staining for BRCA2 mutation carriers (hazards ratio = 7.06; 95% confidence interval = 1.23-40.6; p = 0.028). Poor breast cancer-specific survival of BRCA2 mutation carriers was found to be significantly associated with combined Aurora A nuclear expression and BRCA2 wild type allele loss in tumours (p < 0.001). Multivariate analysis indicated independent prognostic value of both positive Aurora A nuclear staining (hazards ratio = 10.09; 95% confidence interval = 1.19-85.4, p = 0.034) and BRCA2 wild type allele loss (hazards ratio = 9.63; 95% confidence interval = 1.81-51.0, p = 0.008) for BRCA2 mutation carriers. Aurora A nuclear expression was found to be a significant prognostic marker for BRCA2 mutation carriers, independent of clinical parameters and adjuvant treatment. Our conclusion is that treatment benefits for BRCA2 mutation carriers and sporadic breast cancer patients with Aurora A positive tumours may be enhanced by giving attention to Aurora A targeted treatment.

Keywords: Aurora A; BRCA2; adjuvant treatment; breast cancer; prognosis; wild type allele loss.