title: Impact of BMI on serum estradiol and bone turnover markers in postmenopausal women with hormone-sensitive early breast cancer treated with anastrozole.
abstract: OBJECTIVE
  Obesity increases the risk of all-cause and breast cancer mortality. As obese patients have higher levels of aromatase enzyme activity, conflicting results on the effect of body mass index (BMI) of a standard dose aromatase inhibitor on estradiol depletion have been reported.
  
  
  METHODS
  We prospectively investigated the effect of BMI on the efficacy of anastrozole in 70 postmenopausal women with early, ER-positive breast cancer to decrease serum estradiol assessed by a high-sensitive assay with a sensitivity limit of 5 pg/ml over 24 months. Additionally, we examined the changes of bone markers expecting an inverse relationship.
  
  
  RESULTS
  Overall, estradiol decreased from 12.6 pg/ml (SD = 5.4) to 4.0 pg/ml (SD = 5.6) over 24 months (p < 0.001). In contrast, carboxy-terminal collagen crosslinks (CTX) and serum aminoterminal propeptide of type I collagen (PINP) increased from 0.26 ng/ml (SD = 0.18) to 0.40 ng/ml (SD = 0.24) and 41.5 ng/ml (SD = 19.7) to 59.1 ng/ml (SD = 29.1) (p < 0.0001 for both). Baseline estradiol comprised significant differences comparing normal weight with overweight (p < 0.01) or obese patients (p < 0.001). After 12 and 24 months, overweight and obese patients showed a slightly, but insignificantly higher concentrations of estradiol compared to normal weight subjects. We found differences of CTX in comparison between normal weight and obese patients (0.33 vs. 0.21 ng/ml; p < 0.023) at baseline. At 12 and 24 months, there was a significant BMI-independent increase in CTX.
  
  
  CONCLUSIONS
  Estradiol concentrations in postmenopausal women with early, ER-positive breast cancer on anastrozole were significantly different in normal weight versus overweight or obese patients at baseline, but not at 12 and 24 months. CTX and PINP present a notable increase in the first 12 months of anastrozole treatment, stabilizing thereafter.
authors.affiliation: Department of Gynecological Endocrinology, Reproductive Medicine and Osteoporosis, Philipps University of Marburg, Baldingerstr. 1, 35037, Marburg, Germany, janniskyvernitakis@gmail.com.
authors.forename: I
authors.initials: I
authors.lastname: Kyvernitakis
authors.forename: D
authors.initials: D
authors.lastname: Knöll
authors.forename: M
authors.initials: M
authors.lastname: Struck
authors.forename: O
authors.initials: O
authors.lastname: Hars
authors.forename: T
authors.initials: T
authors.lastname: Bauer
authors.forename: P
authors.initials: P
authors.lastname: Hadji
mesh_terms: D000077384:Anastrozole; D047072:Aromatase Inhibitors / Q000627:therapeutic use; D015992:Body Mass Index; D001842:Bone and Bones / Q000378:metabolism; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D024042:Collagen Type I / Q000097:blood*; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009376:Neoplasms, Hormone-Dependent / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D009570:Nitriles / Q000627:therapeutic use*; D009765:Obesity / Q000097:blood / Q000378:metabolism; D050177:Overweight / Q000097:blood / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*; D010455:Peptides / Q000097:blood*; D017698:Postmenopause / Q000097:blood / Q000378:metabolism; D011347:Procollagen / Q000097:blood*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D014230:Triazoles / Q000627:therapeutic use*
chemical_list: D047072:Aromatase Inhibitors; D024042:Collagen Type I; D009570:Nitriles; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; D011960:Receptors, Estrogen; D014230:Triazoles; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000077384:Anastrozole; D004958:Estradiol