title: Sex hormone levels, breast cancer risk, and cancer receptor status in postmenopausal women: the ORDET cohort.
abstract: BACKGROUND
  Endogenous sex hormone levels have been associated with increased breast cancer risk in postmenopausal women in several prospective studies. However, it remains unclear to what extent serum hormone-breast cancer associations differ with receptor status.
  
  
  METHODS
  Associations between serum sex hormone levels and breast cancer risk were assessed in a nested case-control study on postmenopausal women of the ORDET cohort. After a median follow-up of 13.5 years, 165 women developed breast cancer. Relative risks of developing breast cancer were estimated by conditional logistic regression.
  
  
  RESULTS
  Total and free testosterone levels were directly associated with breast cancer risk [relative risk, 3.28 (95% confidence interval, 1.93-5.55) and 2.86 (95% confidence interval, 1.66-4.94), respectively, for highest versus lowest quartile]. When relations between hormone level and risk of breast cancer expressing various receptor combinations were assessed, high total testosterone was significantly associated with increased risk of estrogen receptor-positive cancers, irrespective of progesterone receptor status. High total testosterone was also associated with increased risk of both human epidermal growth factor receptor 2 (HER2)-negative (HER2(-)) and HER2(+) cancers. High estradiol tended to be associated with increased risk of HER2(-) cancer and inversely associated with HER2(+) cancer, with significant (P = 0.027) heterogeneity between HER2(+) and HER2(-) cancers. However, there were relatively few HER2(+) cases.
  
  
  CONCLUSIONS
  This study provides further evidence that high levels of circulating testosterone increase the risk of developing breast cancer in postmenopausal women. The cancers that develop are mainly estrogen receptor positive. Although HER2(+) and HER2(-) breast cancers were both associated with high total testosterone, they showed opposing associations with estrogen.
authors.affiliation: Nutritional Epidemiology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Venezian 1, I-20133 Milan, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Sieri
authors.forename: Vittorio
authors.initials: V
authors.lastname: Krogh
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Bolelli
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Abagnato
authors.forename: Sara
authors.initials: S
authors.lastname: Grioni
authors.forename: Valeria
authors.initials: V
authors.lastname: Pala
authors.forename: Alberto
authors.initials: A
authors.lastname: Evangelista
authors.forename: Claudia
authors.initials: C
authors.lastname: Allemani
authors.forename: Andrea
authors.initials: A
authors.lastname: Micheli
authors.forename: Giovanna
authors.initials: G
authors.lastname: Tagliabue
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Schunemann
authors.forename: Sylvie
authors.initials: S
authors.lastname: Menard
authors.forename: Franco
authors.initials: F
authors.lastname: Berrino
authors.forename: Paola
authors.initials: P
authors.lastname: Muti
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000378:metabolism*; D016022:Case-Control Studies; D004958:Estradiol / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D016015:Logistic Models; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012306:Risk; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: D004958:Estradiol; D012739:Gonadal Steroid Hormones; D018719:Erb-b2 Receptor Tyrosine Kinases; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone