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

Ann Oncol. 2012 Apr;23(4):891-7. doi: 10.1093/annonc/mdr340. Epub 2011 Aug 4.

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.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / surgery
  • CDC2 Protein Kinase / metabolism*
  • Carcinoma, Ductal, Breast / drug therapy
  • Carcinoma, Ductal, Breast / enzymology*
  • Carcinoma, Ductal, Breast / 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*
  • Neoplasm Recurrence, Local / prevention & control
  • Paclitaxel / administration & dosage
  • Receptors, Steroid / metabolism
  • Risk Factors
  • Treatment Outcome

Substances

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