title: Inclusion of endogenous hormone levels in risk prediction models of postmenopausal breast cancer.
abstract: OBJECTIVE
  Endogenous hormones are risk factors for postmenopausal breast cancer, and their measurement may improve our ability to identify high-risk women. Therefore, we evaluated whether inclusion of plasma estradiol, estrone, estrone sulfate, testosterone, dehydroepiandrosterone sulfate, prolactin, and sex hormone-binding globulin (SHBG) improved risk prediction for postmenopausal invasive breast cancer (n = 437 patient cases and n = 775 controls not using postmenopausal hormones) in the Nurses' Health Study.
  
  
  METHODS
  We evaluated improvement in the area under the curve (AUC) for 5-year risk of invasive breast cancer by adding each hormone to the Gail and Rosner-Colditz risk scores. We used stepwise regression to identify the subset of hormones most associated with risk and assessed AUC improvement; we used 10-fold cross validation to assess model overfitting.
  
  
  RESULTS
  Each hormone was associated with breast cancer risk (odds ratio doubling, 0.82 [SHBG] to 1.37 [estrone sulfate]). Individual hormones improved the AUC by 1.3 to 5.2 units relative to the Gail score and 0.3 to 2.9 for the Rosner-Colditz score. Estrone sulfate, testosterone, and prolactin were selected by stepwise regression and increased the AUC by 5.9 units (P = .003) for the Gail score and 3.4 (P = .04) for the Rosner-Colditz score. In cross validation, the average AUC change across the validation data sets was 6.0 (P = .002) and 3.0 units (P = .03), respectively. Similar results were observed for estrogen receptor-positive disease (selected hormones: estrone sulfate, testosterone, prolactin, and SHBG; change in AUC, 8.8 [P < .001] for Gail score and 5.8 [P = .004] for Rosner-Colditz score).
  
  
  CONCLUSIONS
  Our results support that endogenous hormones improve risk prediction for invasive breast cancer and could help identify women who may benefit from chemoprevention or more screening.
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO. nhsst@channing.harvard.edu.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Xuehong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: A Heather
authors.initials: AH
authors.lastname: Eliassen
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Jing
authors.initials: J
authors.lastname: Qian
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Graham A
authors.initials: GA
authors.lastname: Colditz
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Walter C
authors.initials: WC
authors.lastname: Willett
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Peter
authors.initials: P
authors.lastname: Kraft
authors.affiliation: Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, and Susan E. Hankinson, Brigham and Women's Hospital and Harvard Medical School; Shelley S. Tworoger, Xuehong Zhang, A. Heather Eliassen, Walter C. Willett, Bernard A. Rosner, Peter Kraft, and Susan E. Hankinson, Harvard School of Public Health, Boston; Jing Qian and Susan E. Hankinson, School of Public Health and Health Sciences, University of Massachusetts, Amherst, MA; and Graham A. Colditz, Washington University School of Medicine, St Louis, MO.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hankinson
mesh_terms: D000368:Aged; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000031:analogs & derivatives / Q000097:blood; D005260:Female; D006728:Hormones / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D015233:Models, Statistical; D017698:Postmenopause / Q000097:blood*; D011237:Predictive Value of Tests; D011379:Prognosis; D011388:Prolactin / Q000097:blood; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D006728:Hormones; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D011388:Prolactin; C017296:estrone sulfate