title: Effects of aromatase inhibitors and body mass index on steroid hormone levels in women with early and advanced breast cancer.
abstract: BACKGROUND
  Aromatase inhibitors (AIs) are central to the management of oestrogen receptor-positive breast cancer in the adjuvant and metastatic setting. Levels of circulating steroid hormones (SHs) were measured in patients established on AIs to investigate: the influence of body mass index (BMI) in both the adjuvant and metastatic setting; the class of AI utilized in the adjuvant setting (steroidal versus non-steroidal); and differences in SH levels between women treated adjuvantly and those receiving a second-line AI for locally advanced/metastatic disease.
  
  
  METHODS
  Plasma levels of androstenedione, 5-androstene-3β,17β-diol, dehydroepiandrosterone, oestradiol and testosterone were measured by radioimmunoassay in women with breast cancer who were receiving AIs in either an adjuvant or a metastatic setting. Differences between mean SH levels by class of AI, BMI, and second-line versus adjuvant therapy were assessed.
  
  
  RESULTS
  Sixty-four women were receiving AI therapy, 45 (70 per cent) in an adjuvant setting and 19 (30 per cent) were taking a second-line AI. There was no significant correlation between BMI and SH levels. However, BMI was significantly higher in the second-line AI cohort compared with the adjuvant cohort (29.8 versus 26.2 kg/m2 respectively; P = 0.026). In the adjuvant setting, patients receiving a steroidal AI had significantly higher levels of all five hormones (P < 0.050). In the second-line AI cohort, oestradiol levels were significantly higher than in the adjuvant cohort (4.5 versus 3.3 pg/ml respectively; P = 0.022). Multivariable analysis adjusted for BMI confirmed the higher residual oestradiol level in the second-line AI group (P = 0.063) and a significantly higher androstenedione level (P = 0.022).
  
  
  CONCLUSIONS
  Residual levels of SH were not significantly influenced by BMI. However, the significant differences in residual SH levels between the second-line and adjuvant AI cohort is of relevance in the context of resistance to AI therapy, and warrants further investigation.
authors.affiliation: Department of Biosurgery and Surgical Technology, Imperial College London, London, UK; Cancer Research UK Laboratories, Imperial Centre for Translational and Experimental Medicine, Division of Cancer, Imperial College London, London, UK.
authors.forename: K M
authors.initials: KM
authors.lastname: Elliott
authors.forename: J
authors.initials: J
authors.lastname: Dent
authors.forename: F Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: L
authors.initials: L
authors.lastname: Woodley
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
authors.forename: A
authors.initials: A
authors.lastname: Purohit
authors.forename: C
authors.initials: C
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D047072:Aromatase Inhibitors / Q000627:therapeutic use*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D017024:Chemotherapy, Adjuvant; D005260:Female; D042341:Gonadal Hormones / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011863:Radioimmunoassay; D013256:Steroids / Q000378:metabolism*
chemical_list: D047072:Aromatase Inhibitors; D042341:Gonadal Hormones; D013256:Steroids