Recurrence risk score based on the specific activity of CDK1 and CDK2 predicts response to neoadjuvant paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide in breast cancers.

Abstract

BACKGROUND:

We established the cell cycle profiling (C2P) assay for specific activity (SA; activity/expression) of cyclin-dependent kinases (CDKs). C2P risk score (C2P-RS) based on CDK1 and CDK2 SAs was significantly associated with relapse in breast cancer (BC). This study was conducted to investigate the predictive value of C2P-RS for neoadjuvant chemotherapy (NAC).

PATIENTS AND METHODS:

Among 124 eligible patients, 122 were treated with weekly paclitaxel followed by 5-fluorouracil, epirubicin and cyclophosphamide (P-FEC) and 2 were treated with paclitaxel monotherapy. C2P-RS was determined via C2P using frozen biopsy samples before NAC.

RESULTS:

Negative estrogen receptor (ER), negative progesterone receptor (PR), positive human epidermal growth factor receptor 2 (HER2), high Ki-67 expression and intermediate + high C2P-RS were significantly associated with high pathological complete response (pCR) rates compared with positive ER (30% versus 9%), positive PR (25% versus 6%), negative HER2 (34% versus 11%), low Ki-67 expression (24% versus 7%) or low C2P-RS (24% versus 9%), respectively. The combination of C2P-RS and Ki-67 had a stronger impact on pCR than each parameter alone, and a multivariate analysis showed that the combination was an independent predictor of pCR (odds ratio 3.3, 95% confidence interval 1.1-9.5).

CONCLUSIONS:

C2P-RS was significantly associated with pCR after P-FEC and may be a useful predictor for chemotherapy in BCs.

• Authors: S J Kim, S Nakayama, K Shimazu, Y Tamaki, K Akazawa, F Tsukamoto, Y Torikoshi, T Matsushima, M Shibayama, H Ishihara, S Noguchi
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 23 Issue 4 Pg. 891-7 (Apr 2012) ISSN: 1569-8041 [Electronic] England
• PMID: 21821547 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ki-67 Antigen
• Receptors, Steroid
• Epirubicin
• Cyclophosphamide
• CDC2 Protein Kinase
• Cyclin-Dependent Kinase 2
• Paclitaxel
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, enzymology, surgery)
• CDC2 Protein Kinase (metabolism)
• Carcinoma, Ductal, Breast (drug therapy, enzymology, surgery)
• Cyclin-Dependent Kinase 2 (metabolism)
• Cyclophosphamide (administration & dosage)
• Epirubicin (administration & dosage)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Ki-67 Antigen (metabolism)
• Middle Aged
• Multivariate Analysis
• Neoadjuvant Therapy
• Neoplasm Recurrence, Local (enzymology, prevention & control)
• Paclitaxel (administration & dosage)
• Receptors, Steroid (metabolism)
• Risk Factors
• Treatment Outcome