title: Indications of clinical and genetic predictors for aromatase inhibitors related musculoskeletal adverse events in Chinese Han women with breast cancer.
abstract: BACKGROUND
  Women with breast cancer treated with aromatase inhibitors (AIs) may experience musculoskeletal symptoms that lead to discontinuation of effective therapy. The purpose of the current study is to evaluate the clinical and genetic predictors for AIs-related musculoskeletal adverse events(MS-AEs).
  
  
  RESULTS
  We recruited 436 postmenopausal Chinese Han women receiving adjuvant AIs therapy for early-stage hormone-sensitive breast cancer. Patients completed a self-administered questionnaire assessing the presence of musculoskeletal symptoms that started or worsened after initiating AIs. 27 single nucleotide polymorphisms (SNP) of ESR1, ESR2 and PGR were analyzed by Sequenom MassARRAY assays and /or PCR-based TaqMan assays.Of the 436 enrolled women, 206 cases experienced musculoskeletal symptoms.Patients who received taxane chemotherapy were more than two times more likely than other patients to have AIs-related MS-AEs. Genetic assay had showed that only two ESR1 SNPs, rs2234693 and rs9340799 were associated with AIs-related MS-AEs.TT genotype and the T allele in rs2234693 was statistically significantly lower in AIs-Related MS-AEs group than controls (P = 0.001; P = 9.49E-7). The frequency of AA genotype and the A allele in rs9340799 was higher (P = 2.20E-5; P = 3.09E-4).
  
  
  CONCLUSIONS
  Our results suggested that prior taxane-based chemotherapy was the clinical predictor, while rs2234693 and rs9340799 were the genetic predictors for AIs-related MS-AEs.
authors.affiliation: Department of Medical Oncology, The Third Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jingxuan
authors.initials: J
authors.lastname: Wang
authors.forename: Kangping
authors.initials: K
authors.lastname: Lu
authors.forename: Ying
authors.initials: Y
authors.lastname: Song
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Shu
authors.initials: S
authors.lastname: Zhao
authors.forename: Yunxuan
authors.initials: Y
authors.lastname: Wang
authors.forename: Wenzhou
authors.initials: W
authors.lastname: Sun
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.forename: Hong
authors.initials: H
authors.lastname: Zhao
authors.forename: Dabei
authors.initials: D
authors.lastname: Tang
authors.forename: Wenjie
authors.initials: W
authors.lastname: Ma
authors.forename: Bo
authors.initials: B
authors.lastname: Pan
authors.forename: Qijia
authors.initials: Q
authors.lastname: Xuan
authors.forename: Hang
authors.initials: H
authors.lastname: Liu
authors.forename: Qingyuan
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D047072:Aromatase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics*; D001943:Breast Neoplasms / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D001952:Bridged-Ring Compounds / Q000009:adverse effects / Q000627:therapeutic use; D016022:Case-Control Studies; D002681:China; D047628:Estrogen Receptor alpha / Q000235:genetics; D047629:Estrogen Receptor beta / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009140:Musculoskeletal Diseases / Q000209:etiology* / Q000235:genetics; D009367:Neoplasm Staging; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D011980:Receptors, Progesterone / Q000235:genetics; D043823:Taxoids / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D047072:Aromatase Inhibitors; D001952:Bridged-Ring Compounds; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D011980:Receptors, Progesterone; D043823:Taxoids; C080625:taxane
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