title: Combined effects of endogenous sex hormone levels and mammographic density on postmenopausal breast cancer risk: results from the Breakthrough Generations Study.
abstract: BACKGROUND
  Mammographic density and sex hormone levels are strong risk factors for breast cancer, but it is unclear whether they represent the same aetiological entity or are independent risk factors.
  
  
  METHODS
  Within the Breakthrough Generations Study cohort, we conducted a case-control study of 265 postmenopausal breast cancer cases and 343 controls with prediagnostic mammograms and blood samples. Plasma was assayed for oestradiol, testosterone and sex hormone-binding globulin (SHBG) concentrations and mammographic density assessed by Cumulus.
  
  
  RESULTS
  Oestradiol and testosterone were negatively and SHBG positively associated with percentage density and absolute dense area, but after adjusting for body mass index the associations remained significant only for SHBG. Breast cancer risk was independently and significantly positively associated with percentage density (P=0.002), oestradiol (P=0.002) and testosterone (P=0.007) levels. Women in the highest tertile of both density and sex hormone level were at greatest risk, with an odds ratio of 7.81 (95% confidence interval (CI): 2.89-21.1) for oestradiol and 4.57 (95% CI: 1.75-11.9) for testosterone and high density compared with those who were in the lowest tertiles. The cumulative risk of breast cancer in the highest oestradiol and density tertiles, representing 8% of controls, was estimated as 12.8% at ages 50-69 years and 19.4% at ages 20-79 years, and in the lowest tertiles was 1.7% and 4.3%, respectively. Associations of breast cancer risk with tertiles of mammographic dense area were less strong than for percentage density.
  
  
  CONCLUSIONS
  Endogenous sex hormone levels and mammographic density are independent risk factors for postmenopausal breast cancer, which in combination can identify women who might benefit from increased frequency of screening and chemoprophylaxis.
authors: Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, London SM2 5NG, UK.
authors: M J
authors: MJ
authors: Schoemaker
authors: 1] Division of Breast Cancer Research, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [2] Academic Department of Biochemistry, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
authors: E J
authors: EJ
authors: Folkerd
authors: Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, London SM2 5NG, UK.
authors: M E
authors: ME
authors: Jones
authors: 1] Division of Breast Cancer Research, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [2] Academic Department of Biochemistry, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK.
authors: M
authors: M
authors: Rae
authors: Department of Diagnostic Radiology, Royal Marsden Hospital NHS Foundation Trust, Downs Road, London SM2 5PT, UK.
authors: S
authors: S
authors: Allen
authors: 1] Division of Breast Cancer Research, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [2] Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [3] Division of Molecular Pathology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors: A
authors: A
authors: Ashworth
authors: 1] Division of Breast Cancer Research, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [2] Academic Department of Biochemistry, Royal Marsden Hospital NHS Foundation Trust, Fulham Road, London SW3 6JJ, UK [3] Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK [4] Division of Molecular Pathology, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors: M
authors: M
authors: Dowsett
authors: 1] Division of Genetics and Epidemiology, The Institute of Cancer Research, 15 Cotswold Road, London SM2 5NG, UK [2] Division of Breast Cancer Research, The Institute of Cancer Research, 237 Fulham Road, London SW3 6JB, UK.
authors: A J
authors: AJ
authors: Swerdlow
mesh_terms: D000328:Adult; D000368:Aged; D000071060:Breast Density; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology*; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood*; D005260:Female; D006801:Humans; D042361:Mammary Glands, Human / Q000002:abnormalities*; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood / Q000502:physiology; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood*; D055815:Young Adult
chemical_list: D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D004958:Estradiol