title: Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC).
abstract: BACKGROUND
  Contrasting etiologic hypotheses about the role of endogenous sex steroids in breast cancer development among premenopausal women implicate ovarian androgen excess and progesterone deficiency, estrogen excess, estrogen and progesterone excess, and both an excess or lack of adrenal androgens (dehydroepiandrosterone [DHEA] or its sulfate [DHEAS]) as risk factors. We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort to examine associations among premenopausal serum concentrations of sex steroids and subsequent breast cancer risk.
  
  
  METHODS
  Levels of DHEAS, (Delta4-)androstenedione, testosterone, and sex hormone binding globulin (SHBG) were measured in single prediagnostic serum samples from 370 premenopausal women who subsequently developed breast cancer (case patients) and from 726 matched cancer-free control subjects. Levels of progesterone, estrone, and estradiol were also measured for the 285 case patients and 555 matched control subjects who had provided information about the day of menstrual cycle at blood donation. Conditional logistic regression models were used to estimate relative risks of breast cancer by quartiles of hormone concentrations. All statistical tests were two-sided.
  
  
  RESULTS
  Increased risks of breast cancer were associated with elevated serum concentrations of testosterone (odds ratio [OR] for highest versus lowest quartile = 1.73, 95% confidence interval [CI] = 1.16 to 2.57; P(trend) = .01), androstenedione (OR for highest versus lowest quartile = 1.56, 95% CI = 1.05 to 2.32; P(trend) = .01), and DHEAS (OR for highest versus lowest quartile = 1.48, 95% CI = 1.02 to 2.14; P(trend) = .10) but not SHBG. Elevated serum progesterone concentrations were associated with a statistically significant reduction in breast cancer risk (OR for highest versus lowest quartile = 0.61, 95% CI = 0.38 to 0.98; P(trend) = .06). The absolute risk of breast cancer for women younger than 40 followed up for 10 years was estimated at 2.6% for those in the highest quartile of serum testosterone versus 1.5% for those in the lowest quartile; for the highest and lowest quartiles of progesterone, these estimates were 1.7% and 2.6%, respectively. Breast cancer risk was not statistically significantly associated with serum levels of the other hormones.
  
  
  CONCLUSIONS
  Our results support the hypothesis that elevated blood concentrations of androgens are associated with an increased risk of breast cancer in premenopausal women.
authors.affiliation: Nutrition and Hormones Group, International Agency for Research on Cancer (IARC-WHO), Lyon, France. kaaks@iarc.fr
authors.forename: Rudolf
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authors.lastname: Kaaks
authors.forename: Franco
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authors.lastname: Olsen
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Kim
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authors.lastname: Overvad
authors.forename: Domenico
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authors.lastname: Palli
authors.forename: Salvatore
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authors.lastname: Panico
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authors.lastname: Thiebaut
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authors.lastname: Tjønneland
authors.forename: Ma Dolores
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authors.lastname: Chirlaque
authors.forename: Antonia
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authors.lastname: Trichopoulou
authors.forename: Dimitrios
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authors.lastname: Trichopoulos
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Paolo
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authors.lastname: Vineis
authors.forename: Teresa
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authors.lastname: Norat
authors.forename: Pietro
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mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology* / Q000209:etiology; D016022:Case-Control Studies; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D003687:Dehydroepiandrosterone / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005060:Europe / Q000453:epidemiology; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008597:Menstrual Cycle; D008875:Middle Aged; D016017:Odds Ratio; D017697:Premenopause; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate