title: CYP2D6 Genotype and Risk of Recurrence in Tamoxifen Treated Breast Cancer Patients.
abstract: BACKGROUND
  Despite consistent pharmacogenetic effects of CYP2D6 on tamoxifen exposure, there is considerable controversy regarding the validity of CYP2D6 as a predictor of tamoxifen outcome. Understanding the current state of evidence in this area and its limitations is important for the care of patients who require endocrine therapy for breast cancer.
  
  
  METHODS
  A total of 101 patients with breast cancer who received tamoxifen therapy for at least 3 years, were genotyped for common alleles of the CYP2D6 gene by nested-PCR and restriction fragment length polymorphism PCR. Patients were classified as extensive or poor metabolizers (PM) based on CYP2D6*4 alleles in 3 different groups according to the menopause, Her2-neu status, and stage 3.
  
  
  RESULTS
  The mean age of the patients with the disease recurrence was 50.8±6.4 and in non recurrent patients was 48.2±6.8. In this study 63.3% (n=64) patients were extensive metabolizers and 36.6% (n=37) were poor metabolizers. Sixty four of the 101 patients (63.3%) were Her2-neu positive. For tamoxifen- treated patients, no statistically significant difference in rate of recurrence observed between CYP2D6 metabolic variants in stage 3 and post-menopausal patients. However, there was a significant association between CYP2D6 genotype and recurrence in tamoxifen-treated Her2-neu positive patients. Compared with other women with breast cancer, those with Her2-neu positive breast cancer and extensive metabolizer alleles had a decreased likelihood of recurrence.
  
  
  CONCLUSIONS
  This study for the first time demonstrated significant effects of CYP2D6 extensive metabolizer alleles on risk of recurrence in Her2-neu positive breast cancer patients receiving adjuvant tamoxifen therapy. Therefore, CYP2D6 metabolism, as measured by genetic variation, can be a predictor of breast cancer outcome in Her2-neu positive women receiving tamoxifen.
authors.affiliation: Department of Internal Medicine, Shahid Sadoughi Training Hospital, Shahid Sadoughi University of Medical Sciences and Health Services, Yazd, Iran E-mail : hn_1364@yahoo.com.
authors.forename: Mohammad Forat
authors.initials: MF
authors.lastname: Yazdi
authors.forename: Shiva
authors.initials: S
authors.lastname: Rafieian
authors.forename: Mohsen
authors.initials: M
authors.lastname: Gholi-Nataj
authors.forename: Mohammad Hasan
authors.initials: MH
authors.lastname: Sheikhha
authors.forename: Tahereh
authors.initials: T
authors.lastname: Nazari
authors.forename: Hossein
authors.initials: H
authors.lastname: Neamatzadeh
mesh_terms: D000328:Adult; D000483:Alleles; D018931:Antineoplastic Agents, Hormonal / Q000378:metabolism / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002277:Carcinoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000201:enzymology / Q000235:genetics*; D009367:Neoplasm Staging; D012150:Polymorphism, Restriction Fragment Length; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D012307:Risk Factors; D013629:Tamoxifen / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D019389:Cytochrome P-450 CYP2D6; D018719:Erb-b2 Receptor Tyrosine Kinases; D013629:Tamoxifen; C508053:ERBB2 protein, human