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

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.

Figure 1

Aurora A nuclear expression in breast tumours in relation to prognosis. (A) Aurora A nuclear expression was scored negative based on no immunohistochemical nuclear staining (left panel) or positive based on brown peroxidase nuclear staining (right panel). Scale bars = 100 µm. (B) Kaplan‐Meier estimates of breast cancer‐specific survival according to Aurora A nuclear staining in 284 sporadic tumours (left panel) and 107 tumours from BRCA2 mutation carriers (right panel). All statistical tests were two sided.

Figure 2

BRCA2 wild‐type allele loss and Aurora A nuclear expression in breast tumours in relation to prognosis of BRCA2 999del5 mutation carriers. (A) Kaplan‐Meier estimates of breast cancer‐specific survival according to BRCA2 wild‐type allele loss in tumours from 52 BRCA2 mutation carriers. (B) Kaplan‐Meier estimates of breast cancer‐specific survival according to the combination of BRCA2 wild‐type allele loss and Aurora A nuclear staining in tumours from the same subgroup of 52 BRCA2 mutation carriers. All statistical tests were two sided.