title: 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).
  
  
  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.affiliation: Department of Breast and Endocrine Surgery, Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Kim
authors.forename: S
authors.initials: S
authors.lastname: Nakayama
authors.forename: K
authors.initials: K
authors.lastname: Shimazu
authors.forename: Y
authors.initials: Y
authors.lastname: Tamaki
authors.forename: K
authors.initials: K
authors.lastname: Akazawa
authors.forename: F
authors.initials: F
authors.lastname: Tsukamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Torikoshi
authors.forename: T
authors.initials: T
authors.lastname: Matsushima
authors.forename: M
authors.initials: M
authors.lastname: Shibayama
authors.forename: H
authors.initials: H
authors.lastname: Ishihara
authors.forename: S
authors.initials: S
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000201:enzymology* / Q000601:surgery; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D003520:Cyclophosphamide / Q000008:administration & dosage; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000201:enzymology* / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage; D011987:Receptors, Steroid / Q000378:metabolism; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D019394:Ki-67 Antigen; D011987:Receptors, Steroid; D015251:Epirubicin; D003520:Cyclophosphamide; D016203:CDC2 Protein Kinase; D051357:Cyclin-Dependent Kinase 2; D017239:Paclitaxel; D005472:Fluorouracil