title: Sex hormone levels and risks of estrogen receptor-negative and estrogen receptor-positive breast cancers.
abstract: BACKGROUND
  Endogenous sex hormone levels are associated with risks of breast cancer overall and estrogen receptor (ER)-positive breast tumors; however, their associations with ER-negative tumors remain unclear.
  
  
  METHODS
  In a case-cohort study within the Women's Health Initiative Observational Study among postmenopausal women aged 50-79 years, we examined associations between endogenous testosterone and estradiol levels and the risks of ER-negative and ER-positive breast cancers. Serum levels of bioavailable testosterone and estradiol were assessed at the baseline visit in 317 invasive breast cancer case subjects and in a subcohort of 594 women. Bioavailable sex hormone levels were calculated using the total hormone level and the sex hormone-binding globulin concentration (measured by radioimmunoassays and a chemiluminescent immunoassay, respectively). Cox proportional hazards regression was used for statistical analysis. All statistical tests were two-sided.
  
  
  RESULTS
  The unadjusted absolute rates of ER-negative breast cancer for testosterone quartiles 1-4 were 0.34, 0.20, 0.23, and 0.21 per 10,000 person-years, respectively. Compared with women in the lowest quartile of testosterone level, those in quartile 2 had a 56% lower risk of ER-negative cancer (hazard ratio [HR] = 0.44, 95% confidence interval [CI] = 0.23 to 0.85), those in quartile 3 had a 45% lower risk (HR = 0.55, 95% CI = 0.30 to 1.01), and those in quartile 4 had a 49% lower risk (HR = 0.51, 95% CI = 0.28 to 0.94), independent of other risk factors. Estradiol level was not associated with ER-negative breast cancer. ER-positive breast cancer risk increased with higher testosterone levels (P(trend) = .04), but this trend was not statistically significant after adjustment for estradiol (P(trend) = .15). ER-positive cancer risk was approximately twofold higher in women with estradiol levels in quartiles 2-4 compared with women in quartile 1, independent of risk factors.
  
  
  CONCLUSIONS
  Higher serum levels of bioavailable testosterone are associated with lower risks of ER-negative breast cancer in postmenopausal women.
authors.affiliation: San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA 94107, USA. gfarhat@sfcc-cpmc.net
authors.forename: Ghada N
authors.initials: GN
authors.lastname: Farhat
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.forename: Rowan T
authors.initials: RT
authors.lastname: Chlebowski
authors.forename: Neeta
authors.initials: N
authors.lastname: Parimi
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Rohan
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Huang
authors.forename: Mara
authors.initials: M
authors.lastname: Vitolins
authors.forename: F Allan
authors.initials: FA
authors.lastname: Hubbell
authors.forename: Joann E
authors.initials: JE
authors.lastname: Manson
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Cochrane
authors.forename: Dorothy S
authors.initials: DS
authors.lastname: Lane
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Lee
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000097:blood* / Q000737:chemistry*; D016022:Case-Control Studies; D015986:Confounding Factors, Epidemiologic; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D008163:Luminescent Measurements; D008875:Middle Aged; D017698:Postmenopause; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011863:Radioimmunoassay; D011960:Receptors, Estrogen / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol