title: Pharmacogenetic assessment of clinical outcome in patients with metastatic breast cancer treated with docetaxel plus capecitabine.
abstract: OBJECTIVE
  Docetaxel plus capecitabine, a commonly used chemotherapeutic regimen for metastatic breast cancer (MBC), is highly variable in its effectiveness. We aimed to investigate whether allelic variants of cytochrome P450 (CYP450) affected objective response, progression-free survival (PFS), and overall survival (OS) in MBC.
  
  
  METHODS
  79 SNPs in CYP450, whose minor allele frequency were ≥ 10%, were genotyped in 69 MBC patients who were treated with docetaxel plus capecitabine. Pearson's χ(2) test or Fisher's exact test was used to investigate the influence of SNPs on objective response as appropriate. Log-rank test was used to assess the association between SNPs and survival outcomes.
  
  
  RESULTS
  There is no significant association between polymorphisms and both objective response and OS. Only one SNP, CYP1A1 rs1048943 A>G (Ile462Val), was significantly associated with PFS (P = 0.0003). Multivariate analysis confirmed its prognostic significance for PFS (P = 0.004).
  
  
  CONCLUSIONS
  CYP1A1 rs1048943 A>G (Ile462Val) polymorphism is a potential prognostic marker for survival outcome after docetaxel plus capecitabine chemotherapy in MBC patients. However, confirmatory study is needed to validate this finding.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Rd, Haidian District, Beijing 100142, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Dong
authors.forename: Jing
authors.initials: J
authors.lastname: Yu
authors.forename: Chaoying
authors.initials: C
authors.lastname: Wang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Zheng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Di
authors.forename: Guohong
authors.initials: G
authors.lastname: Song
authors.forename: Budong
authors.initials: B
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Che
authors.forename: Jun
authors.initials: J
authors.lastname: Jia
authors.forename: Hanfang
authors.initials: H
authors.lastname: Jiang
authors.forename: Xinna
authors.initials: X
authors.lastname: Zhou
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Ren
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010597:Pharmacogenetics; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D000069287:Capecitabine; D005472:Fluorouracil