title: Premenopausal serum androgens and breast cancer risk: a nested case-control study.
abstract: BACKGROUND
  Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited.
  
  
  METHODS
  A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated.
  
  
  RESULTS
  Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; Ptrend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, Ptrend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls).
  
  
  CONCLUSIONS
  Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.
authors.affiliation: Department of Environmental Medicine, New York University School of Medicine, 650 First Avenue, New York, NY 10016, USA. anne.jacquotte@nyumc.org
authors.forename: Anne
authors.initials: A
authors.lastname: Zeleniuch-Jacquotte
authors.forename: Yelena
authors.initials: Y
authors.lastname: Afanasyeva
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Stephanie
authors.initials: S
authors.lastname: Scarmo
authors.forename: Mengling
authors.initials: M
authors.lastname: Liu
authors.forename: Alan A
authors.initials: AA
authors.lastname: Arslan
authors.forename: Paolo
authors.initials: P
authors.lastname: Toniolo
authors.forename: Roy E
authors.initials: RE
authors.lastname: Shore
authors.forename: Karen L
authors.initials: KL
authors.lastname: Koenig
mesh_terms: D000328:Adult; D000368:Aged; D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood*; D018270:Carcinoma, Ductal, Breast / Q000097:blood*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000097:blood*; D016022:Case-Control Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D016017:Odds Ratio; D017697:Premenopause / Q000097:blood*; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*
chemical_list: D000728:Androgens; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D000735:Androstenedione; D019314:Dehydroepiandrosterone Sulfate