title: Risk of breast cancer in relation to combined effects of hormone therapy, body mass index, and alcohol use, by hormone-receptor status.
abstract: BACKGROUND
  Alcohol consumption, increased body mass index (BMI), and hormone therapy are risk factors for postmenopausal breast cancer, but their combined effects are not well understood. Because hormone therapy is effective for the relief of menopausal symptoms, the identification of "high-risk" users is important for therapeutic reasons. We investigated interactions between hormone therapy use and alcohol-use/high BMI status in relation to invasive breast cancer risk, both overall and according to estrogen receptor (ER) status.
  
  
  METHODS
  Two Danish prospective cohorts were pooled, including 30,789 women ages 50+ years (study period 1981 to 2009). Information on risk factors was obtained in baseline questionnaires. We performed analyses using the Aalen additive hazards model. Serum estradiol and testosterone measurements were obtained in a subsample of approximately 1000 women.
  
  
  RESULTS
  During 392,938 person-years of follow-up, 1579 women developed invasive breast cancer. Among nonusers of hormone therapy, the risk of breast cancer was slightly increased with overweight/obesity and increasing alcohol consumption. Compared with normal-weight nonusers, the risk of breast cancer was higher in hormone therapy users across all BMI strata (P for interaction = 0.003). A markedly higher risk of breast cancer was also observed for alcohol combined with hormone therapy use compared with abstinent nonusers (P for interaction = 0.02). These effects were primarily restricted to ER-positive cases. Combined effects of hormone therapy/high BMI and hormone therapy/alcohol on serum estradiol and testosterone supported the hypothesis of a hormonal pathway linking these exposures to breast cancer.
  
  
  CONCLUSIONS
  These analyses suggest an increased risk of breast cancer associated with hormone therapy use-a risk that may be particularly strong among women consuming alcohol.
authors.affiliation: aSocial Medicine Section, Department of Public Health, University of Copenhagen, Denmark; bDanish Cancer Society Research Centre, Copenhagen, Denmark; cSection of Biostatistics, Department of Public Health, University of Copenhagen, Denmark; dDepartment of Public Health, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Institute of Preventive Medicine, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Frederiksberg, Denmark; eDepartment of Cardiology and The Copenhagen City Heart Study, Bispebjerg and Frederiksberg Hospitals, The Capital Region, Copenhagen, Denmark; fNational Research Centre for the Working Environment, Copenhagen, Denmark; gNational Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; and hDepartment of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev, Denmark.
authors.forename: Ulla Arthur
authors.initials: UA
authors.lastname: Hvidtfeldt
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Niels
authors.initials: N
authors.lastname: Keiding
authors.forename: Theis
authors.initials: T
authors.lastname: Lange
authors.forename: Ingelise
authors.initials: I
authors.lastname: Andersen
authors.forename: Thorkild I A
authors.initials: TI
authors.lastname: Sørensen
authors.forename: Eva
authors.initials: E
authors.lastname: Prescott
authors.forename: Åse Marie
authors.initials: ÅM
authors.lastname: Hansen
authors.forename: Morten
authors.initials: M
authors.lastname: Grønbæk
authors.forename: Stig Egil
authors.initials: SE
authors.lastname: Bojesen
authors.forename: Finn
authors.initials: F
authors.lastname: Diderichsen
authors.forename: Naja Hulvej
authors.initials: NH
authors.lastname: Rod
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000209:etiology*; D003718:Denmark / Q000453:epidemiology; D004958:Estradiol / Q000097:blood; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009765:Obesity / Q000150:complications; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood
chemical_list: D013739:Testosterone; D004958:Estradiol