title: Relationship of body mass index with aromatisation and plasma and tissue oestrogen levels in postmenopausal breast cancer patients treated with aromatase inhibitors.
abstract: BACKGROUND
  Recent data have raised concern about the clinical efficacy of aromatase inhibitors in overweight and/or obese breast cancer patients. We report in vivo aromatase inhibition and plasma and tissue oestrogen levels in relation to body mass index (BMI) status among breast cancer patients treated with different aromatase inhibitors.
  
  
  METHODS
  We compared data on in vivo aromatase inhibition (64 patients) as well as plasma and tissue oestrogen levels from patients participating in our studies to BMI values.
  
  
  RESULTS
  We found a weak positive correlation between pretreatment aromatisation level and BMI (n=64; R=0.236; p=0.060) but no correlation between on-treatment aromatisation levels or percentage aromatase inhibition and BMI within patient subgroups treated with any of a panel of aromatase inhibitors. Pre-treatment levels of plasma estradiol (p<0.001), estrone (p=0.001) and estrone sulphate (p=0.002) correlated to BMI. While on-treatment levels of plasma estrane sulphate correlated to BMI in patients on letrozole (R=0.601; p=0.001; n=25 for all) or anastrozole (n=12; R=0.611; p=0.035) therapy, letrozole suppressed plasma estrone sulphate more than anastrozole independent of BMI. No correlation between on-treatment tumour oestrogen levels and BMI was recorded.
  
  
  CONCLUSIONS
  Our unique data do not support a lack of effective aromatase inhibition in overweight patients or therefore a need for alternative therapy. The higher levels of estrogens in overweight postmenopausal breast cancer patients before and during aromatase inhibition may be due to effects of BMI on oestrogen metabolism rather than aromatisation.
authors: Section of Oncology, Department of Medicine, University of Bergen, Bergen, Norway; Department of Oncology, Haukeland University Hospital, Bergen, Norway. Electronic address: per.lonning@helse-bergen.no.
authors: Per Eystein
authors: PE
authors: Lønning
authors: Academic Department of Biochemistry, Royal Marsden Hospital, London, UK.
authors: Benjamin P
authors: BP
authors: Haynes
authors: Academic Department of Biochemistry, Royal Marsden Hospital, London, UK; Breakthrough Breast Cancer Research Centre, Institute of Cancer Research, London, UK.
authors: Mitch
authors: M
authors: Dowsett
mesh_terms: D000368:Aged; D000077384:Anastrozole; D000728:Androgens / Q000097:blood; D001141:Aromatase / Q000378:metabolism; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004958:Estradiol / Q000097:blood; D004967:Estrogens / Q000032:analysis* / Q000097:blood / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D017063:Outcome Assessment, Health Care / Q000379:methods; D017698:Postmenopause; D014230:Triazoles / Q000627:therapeutic use
chemical_list: D000728:Androgens; D047072:Aromatase Inhibitors; D004967:Estrogens; D009570:Nitriles; D014230:Triazoles; D004970:Estrone; D000077384:Anastrozole; D004958:Estradiol; D000077289:Letrozole; D001141:Aromatase; C017296:estrone sulfate
keywords: Aromatase; BMI; Breast cancer; Endocrine therapy; Estradiol; Obesity; Overweight