title: Effects of CYP2B6 genetic polymorphisms in patients receiving cyclophosphamide combination chemotherapy for breast cancer.
abstract: OBJECTIVE
  The purpose of this study was to measure the frequency of three CYP2B6 [CYP2B6*4 (rs2279343), CYP2B6*5 (rs3211371) and CYP2B6*9 (rs3745274)] alleles in patients with breast cancer receiving cyclophosphamide (CP) therapy and test whether these variants are predictors of CP-associated toxicity and efficacy.
  
  
  METHODS
  A total of 145 female breast cancer patients admitted to the American University of Beirut Medical Center for breast cancer-related therapy were included. Chart review was performed for collection of toxicity data. A time-to-event analysis was performed with a subset of 38 patients.
  
  
  RESULTS
  The minor allele frequencies of CYP2B6*9, CYP2B6*4 and CYP2B6*5 were 0.27, 0.29 and 0.07, respectively. CYP2B6 *5/*6, *6/*9 or *6/*6 haplotypes were associated with a significantly shorter time to recurrence of the disease. There were no significant associations with myelo-toxicity.
  
  
  CONCLUSIONS
  This is the first report on the pharmacogenetic profile of patients with breast cancer and the therapeutic and myelo-toxic behavior of CP in women from an Arab Middle Eastern country. Our results show that genotyping for these CYP2B6 alleles does not help in personalizing therapy from a toxicity perspective, and the association of shorter survival in these subjects with homozygous variants is interesting yet insufficient to justify routine genotyping prior to therapy, or to consider using a higher CP dose. Larger future studies or meta-analyses will be needed to further clarify the potential implication of these genetic polymorphisms.
authors.affiliation: Division of Hematology and Oncology, Department of Internal Medicine, School of Medicine, George Washington University, Washington, DC, USA.
authors.forename: F
authors.initials: F
authors.lastname: Haroun
authors.forename: L
authors.initials: L
authors.lastname: Al-Shaar
authors.forename: R H
authors.initials: RH
authors.lastname: Habib
authors.forename: N
authors.initials: N
authors.lastname: El-Saghir
authors.forename: A
authors.initials: A
authors.lastname: Tfayli
authors.forename: A
authors.initials: A
authors.lastname: Bazarbachi
authors.forename: Z
authors.initials: Z
authors.lastname: Salem
authors.forename: A
authors.initials: A
authors.lastname: Shamseddine
authors.forename: A
authors.initials: A
authors.lastname: Taher
authors.forename: I
authors.initials: I
authors.lastname: Cascorbi
authors.forename: N K
authors.initials: NK
authors.lastname: Zgheib
mesh_terms: D000328:Adult; D000483:Alleles; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D065702:Cytochrome P-450 CYP2B6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D006801:Humans; D007861:Lebanon; D008875:Middle Aged; D038042:Myelopoiesis / Q000187:drug effects; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6