title: Sex hormones and risk of breast cancer in premenopausal women: a collaborative reanalysis of individual participant data from seven prospective studies.
abstract: BACKGROUND
  Associations between circulating concentrations of oestrogens, progesterone, and androgens with breast cancer and related risk factors in premenopausal women are not well understood. We aimed to characterise these associations with a pooled analysis of data from seven studies.
  
  
  METHODS
  Individual participant data for prediagnostic sex hormone and sex hormone-binding globulin (SHBG) concentrations were contributed from seven prospective studies. We restricted analyses to women who were premenopausal and younger than 50 years at blood collection, and to women with breast cancer diagnosed before age 50 years. We estimated odds ratios (ORs) with 95% CIs for breast cancer associated with hormone concentrations by conditional logistic regression in cases and controls matched for age, date of blood collection, and day of cycle, with stratification by study and further adjustment for cycle phase. We examined associations of hormones with risk factors for breast cancer in control women by comparing geometric mean hormone concentrations in categories of these risk factors, adjusted for study, age, phase of menstrual cycle, and body-mass index (BMI). All statistical tests were two-sided.
  
  
  RESULTS
  We included data for up to 767 women with breast cancer and 1699 controls in the risk analyses. Breast cancer risk was associated with a doubling in concentrations of oestradiol (OR 1·19, 95% CI 1·06-1·35), calculated free oestradiol (1·17, 1·03-1·33), oestrone (1·27, 1·05-1·54), androstenedione (1·30, 1·10-1·55), dehydroepiandrosterone sulphate (1·17, 1·04-1·32), testosterone (1·18, 1·03-1·35), and calculated free testosterone (1·08, 0·97-1·21). Breast cancer risk was not associated with luteal phase progesterone (doubling in concentration OR 1·00, 95% CI 0·92-1·09), and adjustment for other factors had little effect on any of these ORs. Cross-sectional analyses in control women showed several associations of sex hormones with breast cancer risk factors.
  
  
  CONCLUSIONS
  Circulating oestrogens and androgens are positively associated with the risk for breast cancer in premenopausal women.
authors.forename: T J
authors.initials: TJ
authors.lastname: Key
authors.forename: P N
authors.initials: PN
authors.lastname: Appleby
authors.forename: G K
authors.initials: GK
authors.lastname: Reeves
authors.forename: R C
authors.initials: RC
authors.lastname: Travis
authors.forename: A J
authors.initials: AJ
authors.lastname: Alberg
authors.forename: A
authors.initials: A
authors.lastname: Barricarte
authors.forename: F
authors.initials: F
authors.lastname: Berrino
authors.forename: V
authors.initials: V
authors.lastname: Krogh
authors.forename: S
authors.initials: S
authors.lastname: Sieri
authors.forename: L A
authors.initials: LA
authors.lastname: Brinton
authors.forename: J F
authors.initials: JF
authors.lastname: Dorgan
authors.forename: L
authors.initials: L
authors.lastname: Dossus
authors.forename: M
authors.initials: M
authors.lastname: Dowsett
authors.forename: A H
authors.initials: AH
authors.lastname: Eliassen
authors.forename: R T
authors.initials: RT
authors.lastname: Fortner
authors.forename: S E
authors.initials: SE
authors.lastname: Hankinson
authors.forename: K J
authors.initials: KJ
authors.lastname: Helzlsouer
authors.forename: J
authors.initials: J
authors.lastname: Hoff man-Bolton
authors.forename: George W
authors.initials: GW
authors.lastname: Comstock
authors.forename: R
authors.initials: R
authors.lastname: Kaaks
authors.forename: L L
authors.initials: LL
authors.lastname: Kahle
authors.forename: P
authors.initials: P
authors.lastname: Muti
authors.forename: K
authors.initials: K
authors.lastname: Overvad
authors.forename: P H M
authors.initials: PH
authors.lastname: Peeters
authors.forename: E
authors.initials: E
authors.lastname: Riboli
authors.forename: S
authors.initials: S
authors.lastname: Rinaldi
authors.forename: D E
authors.initials: DE
authors.lastname: Rollison
authors.forename: F Z
authors.initials: FZ
authors.lastname: Stanczyk
authors.forename: D
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: S S
authors.initials: SS
authors.lastname: Tworoger
authors.forename: P
authors.initials: P
authors.lastname: Vineis
mesh_terms: D000328:Adult; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood / Q000209:etiology*; D003299:Cooperative Behavior; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D017697:Premenopause; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis
chemical_list: D012739:Gonadal Steroid Hormones; D012738:Sex Hormone-Binding Globulin; D019314:Dehydroepiandrosterone Sulfate
references.citation: Endocr Relat Cancer. 2005 Dec;12(4):1071-82
references.pmid: 16322344
references.citation: J Natl Cancer Inst. 1980 Jul;65(1):43-6
references.pmid: 6930516
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Dec;12(12):1457-61
references.pmid: 14693737
references.citation: Eur J Cancer Clin Oncol. 1988 Jan;24(1):29-43
references.pmid: 3276531
references.citation: Br J Cancer. 1997;75(7):1075-9
references.pmid: 9083346
references.citation: Breast Cancer Res. 2010;12(6):R98
references.pmid: 21087481
references.citation: J Natl Cancer Inst. 2002 Apr 17;94(8):606-16
references.pmid: 11959894
references.citation: Cancer Epidemiol Biomarkers Prev. 1996 Nov;5(11):917-22
references.pmid: 8922301
references.citation: Clin Endocrinol (Oxf). 1980 Apr;12(4):363-9
references.pmid: 6769612
references.citation: J Steroid Biochem. 1982 Jun;16(6):801-10
references.pmid: 7202083
references.citation: Breast Cancer Res Treat. 2013 Feb;137(3):883-92
references.pmid: 23283524
references.citation: Am J Epidemiol. 2000 Sep 15;152(6):514-27
references.pmid: 10997541
references.citation: Breast Cancer Res. 2012 Feb 16;14(1):R32
references.pmid: 22339988
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):492-502
references.pmid: 20086116
references.citation: J Natl Cancer Inst. 1973 Jan;50(1):21-42
references.pmid: 4571238
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):967-71
references.pmid: 16702378
references.citation: Int J Obes (Lond). 2013 Feb;37(2):237-43
references.pmid: 22310471
references.citation: Am J Obstet Gynecol. 1978 Feb 15;130(4):456-61
references.pmid: 629290
references.citation: Horm Behav. 2010 Jun;58(1):57-71
references.pmid: 19835877
references.citation: J Natl Cancer Inst. 2006 Oct 4;98(19):1406-15
references.pmid: 17018787
references.citation: Br J Cancer. 2011 Aug 23;105(5):709-22
references.pmid: 21772329
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Apr;19(4):960-5
references.pmid: 20233851
references.citation: Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):972-8
references.pmid: 16702379
references.citation: Br J Cancer. 2011 Sep 27;105(7):911-7
references.pmid: 21897394
references.citation: Am J Epidemiol. 1987 May;125(5):791-9
references.pmid: 3565354
references.citation: Cancer Detect Prev. 1994;18(2):79-85
references.pmid: 8025899
references.citation: Int J Cancer. 2004 Nov 1;112(2):312-8
references.pmid: 15352045
references.citation: Int J Cancer. 1989 Nov 15;44(5):783-7
references.pmid: 2511157
references.citation: Breast Cancer Res. 2013 Mar 06;15(2):R19
references.pmid: 23497468
references.citation: Epidemiology. 1994 Mar;5(2):247-50
references.pmid: 8173001
references.citation: J Natl Cancer Inst. 2005 May 18;97(10):755-65
references.pmid: 15900045
references.citation: Br J Cancer. 2002 Nov 18;87(11):1234-45
references.pmid: 12439712
references.citation: J Chronic Dis. 1987;40(11):995-1002
references.pmid: 3654908
references.citation: Clin Sci (Lond). 1984 Apr;66(4):369-76
references.pmid: 6365407
references.citation: Cancer Epidemiol Biomarkers Prev. 2000 Jun;9(6):575-9
references.pmid: 10868691
references.citation: Radiat Res. 2011 Nov;176(5):678-87
references.pmid: 21718103
references.citation: Lancet. 2012 Mar 31;379(9822):1173-4
references.pmid: 22463865
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Sep;16(9):1713-9
references.pmid: 17855686
references.citation: Cancer Res. 1992 Jan 1;52(1):1-4
references.pmid: 1530765