title: Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status - results from the EPIC cohort.
abstract: Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1  = 1.56 (95% CI 1.15-2.13), ptrend  = 0.02 for testosterone and ORQ4-Q1  = 1.33 (95% CI 0.99-1.79), ptrend  = 0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1  = 1.32 (95% CI 0.87-2.01), ptrend  = 0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1  = 0.94 (95% CI 0.60-1.47), ptrend  = 0.34, phet  = 0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Kaja
authors.initials: K
authors.lastname: Tikk
authors.forename: Disorn
authors.initials: D
authors.lastname: Sookthai
authors.forename: Helena
authors.initials: H
authors.lastname: Schock
authors.forename: Theron
authors.initials: T
authors.lastname: Johnson
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Françoise
authors.initials: F
authors.lastname: Clavel-Chapelon
authors.forename: Laure
authors.initials: L
authors.lastname: Dossus
authors.forename: Laura
authors.initials: L
authors.lastname: Baglietto
authors.forename: Sabina
authors.initials: S
authors.lastname: Rinaldi
authors.forename: Veronique
authors.initials: V
authors.lastname: Chajes
authors.forename: Isabelle
authors.initials: I
authors.lastname: Romieu
authors.forename: Heiner
authors.initials: H
authors.lastname: Boeing
authors.forename: Madlen
authors.initials: M
authors.lastname: Schütze
authors.forename: Antonia
authors.initials: A
authors.lastname: Trichopoulou
authors.forename: Pagona
authors.initials: P
authors.lastname: Lagiou
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Trichopoulos
authors.forename: Domenico
authors.initials: D
authors.lastname: Palli
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.forename: Rosario
authors.initials: R
authors.lastname: Tumino
authors.forename: Fulvio
authors.initials: F
authors.lastname: Ricceri
authors.forename: Amalia
authors.initials: A
authors.lastname: Mattiello
authors.forename: Genevieve
authors.initials: G
authors.lastname: Buckland
authors.forename: Jose
authors.initials: J
authors.lastname: Ramón Quirós
authors.forename: María-José
authors.initials: MJ
authors.lastname: Sánchez
authors.forename: Pilar
authors.initials: P
authors.lastname: Amiano
authors.forename: Maria-Dolores
authors.initials: MD
authors.lastname: Chirlaque
authors.forename: Aurelio
authors.initials: A
authors.lastname: Barricarte
authors.forename: H
authors.initials: H
authors.lastname: Bas Bueno-de-Mesquita
authors.forename: Carla H
authors.initials: CH
authors.lastname: van Gils
authors.forename: Petra H
authors.initials: PH
authors.lastname: Peeters
authors.forename: Anne
authors.initials: A
authors.lastname: Andersson
authors.forename: Malin
authors.initials: M
authors.lastname: Sund
authors.forename: Elisabete
authors.initials: E
authors.lastname: Weiderpass
authors.forename: Kay-Tee
authors.initials: KT
authors.lastname: Khaw
authors.forename: Nick
authors.initials: N
authors.lastname: Wareham
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Key
authors.forename: Ruth C
authors.initials: RC
authors.lastname: Travis
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Merritt
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Gunter
authors.forename: Elio
authors.initials: E
authors.lastname: Riboli
authors.forename: Annekatrin
authors.initials: A
authors.lastname: Lukanova
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000097:blood* / Q000453:epidemiology*; D016022:Case-Control Studies; D015331:Cohort Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017697:Premenopause / Q000097:blood; D011374:Progesterone / Q000097:blood; D011446:Prospective Studies; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D004958:Estradiol; D012739:Gonadal Steroid Hormones; D011374:Progesterone; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; C508053:ERBB2 protein, human
keywords: EPIC; breast cancer; estrogen receptor; prospective cohort; sex hormones