Determination of the specific activity of CDK1 and CDK2 as a novel prognostic indicator for early breast cancer

Background: We recently established a novel assay for specific activity (SA) of cyclin-dependent kinases (CDKs) using small tumor samples ( :8 MM). The aim of this study was to investigate the prognostic significance of CDK1SA and CDK2SA in human breast cancer. Methods: CDK1SA and CDK2SA were determined in 284 breast cancer patients and their prognostic significance was investigated. Results: Tumors with high CDK1SA and high CDK2SA showed significantly poorer 5-year relapse-free survival than those with low CDK1 SA and low CDK2SA, respectively (66.9% vs 84.2% for CDK1SA; 43.6% vs 83.6% for CDK2SA). Moreover, combined analysis of CDK1SA and CDK2SA enabled the classification of breast tumors into high-risk and low-risk groups, where tumors in the high-risk group were strongly associated with unfavorable prognosis (5-year relapse-free survival 69.4% for the high-risk group and 91.5% for the low-risk group). Multivariate analysis showed that the risk determined by combined analysis of CDK1 SA and CDK2SA is a significant (hazard ratio 3.09, P < 0.001) prognostic indicator for relapse, especially in node-negative patients (hazard ratio 6.73, P < 0.001). Conclusion: Determination of CDK1 SA and CDK2SA may be useful in the prediction of outcomes in breast cancer patients and has potential for use as a routine laboratory test.