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(3)). 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 CDK1SA 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 CDK1SA 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).


CONCLUSIONS
Determination of CDK1SA and CDK2SA may be useful in the prediction of outcomes in breast cancer patients and has potential for use as a routine laboratory test.
Kim
S J
SJ
Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Japan.
Nakayama
S
S
Miyoshi
Y
Y
Taguchi
T
T
Tamaki
Y
Y
Matsushima
T
T
Torikoshi
Y
Y
Tanaka
S
S
Yoshida
T
T
Ishihara
H
H
Noguchi
S
S
D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D016203:CDC2 Protein Kinase / Q000032:analysis*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality / Q000601:surgery; D003131:Combined Modality Therapy; D051357:Cyclin-Dependent Kinase 2 / Q000032:analysis*; D018572:Disease-Free Survival; D004967:Estrogens; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008408:Mastectomy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000201:enzymology / Q000401:mortality / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D012306:Risk
D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D004967:Estrogens; D009363:Neoplasm Proteins; D016203:CDC2 Protein Kinase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2