HR Ali, S-J Dawson, FM Blows, E Provenzano, PD Pharoah, C Caldas
Br J Cancer
BACKGROUND: Proliferation has emerged as a major prognostic factor in luminal breast cancer. The immunohistochemical (IHC) proliferation marker Ki67 has been most extensively investigated but has not gained widespread clinical acceptance. METHODS: We have conducted a head-to-head comparison of a panel of proliferation markers, including Ki67. Our aim was to establish the marker of the greatest prognostic utility. Tumour samples from 3093 women with breast cancer were constructed as tissue microarrays. We used IHC to detect expression of mini-chromosome maintenance protein 2, Ki67, aurora kinase A (AURKA), polo-like kinase 1, geminin and phospho-histone H3. We used a Cox proportional-hazards model to investigate the association with 10-year breast cancer-specific survival (BCSS). Missing values were resolved using multiple imputation. RESULTS: The prognostic significance of proliferation was limited to oestrogen receptor (ER)-positive breast cancer. Aurora kinase A emerged as the marker of the greatest prognostic significance in a multivariate model adjusted for the standard clinical and molecular covariates (hazard ratio 1.3; 95% confidence interval 1.1-1.5; P=0.005), outperforming all other markers including Ki67. CONCLUSION: Aurora kinase A outperforms other proliferation markers as an independent predictor of BCSS in ER-positive breast cancer. It has the potential for use in routine clinical practice.