Validation study of the prognostic value of cyclin-dependent kinase (CDK)-based risk in Caucasian breast cancer patients

Abstract

In a Japanese study, cyclin-dependent kinase (CDK) based risk determined by CDK 1 and 2 activities was associated with risk of distance recurrence in early breast cancer patients. The aim of our study was to validate this risk categorization in European early breast cancer patients. We retrospectively analyzed frozen breast cancer specimens of 352 Dutch patients with histologically confirmed primary invasive early breast cancer. CDK-based risk was determined in tumour tissues by calculating a risk score (RS) according to kinases activity and protein mass concentration assay without the knowledge of outcome. Determination of CDK-based risk was feasible in 184 out of 352 (52%) tumours. Median follow-up of these patients was 15 years. In patients not receiving systemic treatment, the proportions of risk categories were 44% low, 16% intermediate, and 40% high CDK-based risk. These groups remained significant after univariate and multivariate Cox-regression analysis. Factors associated with a shorter distant recurrence-free period were positive lymph nodes, mastectomy with radiotherapy, and high CDK-based risk. There was no significant correlation with overall survival (OS). CDK-based risk is a prognostic marker of distance recurrence of patients with early breast cancer. More validation would be warranted to use of CDK-based risk into clinical practice.

Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression

“…CDK4 kinase activity was measured with the non-radioisotopic C2P system (Sysmex, Kobe, Japan) as described previously [19]. Protein lysate was applied to a well of a dot-blot device.…”

CDK1 and CDK2 activity is a strong predictor of renal cell carcinoma recurrence

“…Recently, we succeeded in developing a system that can assay the specific activity (SA) of CDKs using small tissue samples [12]. The clinical utility of the technology was first evaluated in breast cancer, and combination analysis of CDK1 and CDK2 activity was shown to be a significant prognostic indicator for relapse [13,14]. The objective of this study was to clarify the prognostic implications of CDKSA in RCCs.…”

Cyclin-dependent kinase-specific activity predicts the prognosis of stage I and stage II non-small cell lung cancer

“…The C2P® assay is determined using a combination of the specific activity of CDK1 (CDK1SA) and CDK2 (CDK2SA). The feasibility of this assay was confirmed in a cohort study in Caucasian breast cancer patients [ 23 ] and in colon cancer patients [ 24 ]. CDKSAs were also significantly associated with a pathologically complete response (pCR) after weekly administration of paclitaxel followed by 5-fluorouracil, epirubicin, and cyclophosphamide in breast cancer [ 25 ].…”