title: Estrogens and their precursors in postmenopausal women with early breast cancer receiving anastrozole.
abstract: OBJECTIVE
  We determined hormone concentrations (estradiol [E2], estrone [E1], estrone conjugates [E1-C], androstenedione [A], testosterone [T]) before and on anastrozole therapy where we also determined plasma concentrations of anastrozole and its metabolites.
  
  
  METHODS
  Postmenopausal women who were to receive adjuvant anastrozole for resected early breast cancer were studied. Pretreatment, blood samples were obtained for the acquisition of DNA and for plasma hormone measurements (E2, E1, E1-C, A, and T). A second blood draw was obtained at least 4 weeks after starting anastrozole for hormone, anastrozole and metabolite measurements. For hormone assays, a validated bioanalytical method using gas chromatography negative ionization tandem mass spectrometry was used. Anastrozole and metabolite assays involved extraction of plasma followed by LC/MS/MS assays.
  
  
  RESULTS
  649 patients were evaluable. Pretreatment and during anastrozole, there was large inter-individual variability in E2, E1, and E1-C as well as anastrozole and anastrozole metabolite concentrations. E2 and E1 concentrations were below the lower limits of quantitation in 79% and 70%, respectively, of patients on anastrozole therapy, but those with reliable concentrations had a broad range (0.627-234.0 pg/mL, 1.562-183.2 pg/mL, respectively). Considering E2, 8.9% had the same or higher concentration relative to baseline while on anastrozole, documented by the presence of drug.
  
  
  CONCLUSIONS
  We demonstrated large inter-individual variability in anastrozole and anastrozole metabolite concentrations as well as E1, E2, E1-C, A, and T concentrations before and while on anastrozole. These findings suggest that the standard 1mg daily dose of anastrozole is not optimal for a substantial proportion of women with breast cancer.
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, MN, United States. Electronic address: ingle.james@mayo.edu.
authors.forename: James N
authors.initials: JN
authors.lastname: Ingle
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States.
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Kalari
authors.affiliation: Department of Breast Oncology, M.D. Anderson Cancer Center, Houston, TX, United States.
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.affiliation: Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Robson
authors.affiliation: Division of Medical Oncology, Mayo Clinic, Rochester, MN, United States.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Goetz
authors.affiliation: Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: Zeruesenay
authors.initials: Z
authors.lastname: Desta
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, United States.
authors.forename: Poulami
authors.initials: P
authors.lastname: Barman
authors.affiliation: Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States.
authors.forename: Tanda T
authors.initials: TT
authors.lastname: Dudenkov
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Scottsdale, AZ, United States.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Northfelt
authors.affiliation: Division of Hematology/Oncology, Mayo Clinic, Jacksonville, FL, United States.
authors.forename: Edith A
authors.initials: EA
authors.lastname: Perez
authors.affiliation: Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN, United States.
authors.forename: David A
authors.initials: DA
authors.lastname: Flockhart
authors.affiliation: inVentiv Health, Princeton, NJ, United States.
authors.forename: Clark V
authors.initials: CV
authors.lastname: Williard
authors.affiliation: Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States.
authors.forename: Liewei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Division of Clinical Pharmacology, Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, United States.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Weinshilboum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077384:Anastrozole; D000735:Androstenedione / Q000097:blood; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000097:blood*; D004970:Estrone / Q000097:blood; D005260:Female; D006801:Humans; D008875:Middle Aged; D009570:Nitriles / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D017698:Postmenopause / Q000097:blood / Q000187:drug effects*; D013739:Testosterone / Q000097:blood; D014230:Triazoles / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol
keywords: Anastrozole; Androstenedione; Estradiol; Estrone; Estrone conjugates; Testosterone