title: S4646 polymorphism in CYP19A1 gene is associated with the efficacy of hormone therapy in early breast cancer.
abstract: OBJECTIVE
  The aim was to verify the potential association between CYP19A1 genetic polymorphisms and clinical outcome of hormone therapy in hormone receptor (HR)-positive early breast cancer.
  
  
  METHODS
  Genotyping for CYP19A1 rs4646 (C/A) polymorphism was performed on 287 women with HR-positive early breast cancer. Associations were evaluated between CYP19A1 rs4646 genotypes and disease-free survival (DFS).
  
  
  RESULTS
  Totally, women with the minor allele (AA or AC) had an improved DFS when compared with those carrying the homozygous common allele (CC) (AA or AC vs. CC: 62.7 months versus 55.6 months; Hazard ratio (HR), 0.745; 95% CI, 0.562-0.988; P=0.04). The difference was further demonstrated by multivariate analyses (HR, 0.681; 95% CI, 0.506-0.917; P=0.011). In premenopausal women, AA genotype was associated with a prolonged DFS (AA versus CC or AC: 98.2 months versus 56.2 months; HR, 0.425; 95% CI, 0.198-0.914; P=0.024). In addition, women with the A allele had an improved DFS when compared with those carrying the homozygous C allele (AA or AC vs. CC: 62.7 months versus 55.6 months; HR, 0.709; 95% CI, 0.516-0.975; P=0.033). These findings were further confirmed by the Cox regression model (HR, 0.336, 0.670; 95% CI, 0.160-0.836, 0.479-0.938; P=0.017, 0.019). In postmenopausal women, rs4646 genotypes were significantly associated with DFS (AA versus AC versus CC: 32.7 months versus not reached versus 56.3 months; P=0.011). Women carrying AA variant had a poorer DFS than those with CC or AC genotypes (32.7 months versus 70.6 months; HR, 3.613; 95% CI, 1.380-9.457; P=0.005). Furthermore, being adjusted by the patients features in multivariate analyses, AA genotype remained an independent prognostic factor for DFS (HR, 3.614; 95% CI, 1.308-9.991; P=0.013).
  
  
  CONCLUSIONS
  The homozygous minor allele (AA) of CYP19A1 rs4646 is significantly associated with improved clinical outcome of hormone therapy in premenopausal HR-positive early breast cancer patients, but with a worse impact on postmenopausal women. The findings are novel, if confirmed, genotyping for CYP19A1 rs4646 polymorphism may provide predictive information for better selection of endocrine treatment.
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Xiying
authors.initials: X
authors.lastname: Shao
authors.affiliation: Department of Oncology, People's Hospital of Kecheng District Quzhou, Zhejiang Province, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Yabing
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou, Zhejiang Province, China.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Wang
authors.affiliation: Cancer Research Institute, Zhejiang Cancer Hospital Hangzhou, Zhejiang Province, China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Zhanhong
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Zhejiang Traditional Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Medical Oncology, Affiliated Zhejiang Cancer Hospital of Zhejiang Chinese Medical University Hangzhou, Zhejiang Province, China.
authors.forename: Xiaojia
authors.initials: X
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001141:Aromatase / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D016009:Chi-Square Distribution; D018572:Disease-Free Survival; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000401:mortality; D018579:Patient Selection; D010597:Pharmacogenetics; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D057285:Precision Medicine; D017697:Premenopause; D016016:Proportional Hazards Models; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018931:Antineoplastic Agents, Hormonal; D001141:Aromatase; C561410:CYP19A1 protein, human
keywords: Breast cancer; aromatase; genetic polymorphisms; predictive role