title: Association of serum sex steroid receptor bioactivity and sex steroid hormones with breast cancer risk in postmenopausal women.
abstract: Postmenopausal women with elevated serum sex steroids have an increased risk of breast cancer. Most of this risk is believed to be exerted through binding of the sex steroids to their receptors. For the first time, we investigate the association of estrogen receptor (ER) and androgen receptor (AR) serum bioactivity (SB) in addition to hormone levels in samples from women with breast cancer collected before diagnosis. Two hundred postmenopausal women participating in the UK Collaborative Trial of Ovarian Cancer Screening who developed ER-positive breast cancer 0.6-5 years after sample donation were identified and matched to 400 controls. ER and AR bioassays were used to measure ERα, ERβ, and AR SB. Androgen and estrogen levels were measured with immunoassays. Subjects were classified according to quintiles of the respective marker among controls and the associations between SB and hormones with breast cancer risk were determined by logistic regression analysis. ERα and ERβ SB were significantly higher before diagnosis compared with controls, while estrogens showed no difference. Women had a twofold increased breast cancer risk if ERα SB (odds ratio (OR), 2.114; 95% confidence interval (CI), 1.050-4.425; P=0.040) was in the top quintile >2 years before diagnosis or estrone (OR, 2.205; 95% CI, 1.104-4.586; P=0.029) was in the top quintile <2 years before diagnosis. AR showed no significant association with breast cancer while androstenedione (OR, 3.187; 95% CI, 1.738-6.044; P=0.0003) and testosterone (OR, 2.145; 95% CI, 1.256-3.712; P=0.006) were significantly higher compared with controls and showed a strong association with an almost threefold increased breast cancer risk independent of time to diagnosis. This study provides further evidence on the association of androgens and estrogens with breast cancer. In addition, it reports that high ER but not AR SB is associated with increased breast risk >2 years before diagnosis.
authors.affiliation: Department of Gynecological Oncology, Institute for Women's Health, Gynecological Cancer Research Centre, University College London, London, UK. e.fourkala@ucl.ac.uk
authors.forename: Evangelia-Ourania
authors.initials: EO
authors.lastname: Fourkala
authors.forename: Alexey
authors.initials: A
authors.lastname: Zaikin
authors.forename: Matthew
authors.initials: M
authors.lastname: Burnell
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: Jeremy
authors.initials: J
authors.lastname: Ford
authors.forename: Richard
authors.initials: R
authors.lastname: Gunu
authors.forename: Christina
authors.initials: C
authors.lastname: Soromani
authors.forename: Guido
authors.initials: G
authors.lastname: Hasenbrink
authors.forename: Ian
authors.initials: I
authors.lastname: Jacobs
authors.forename: Anne
authors.initials: A
authors.lastname: Dawnay
authors.forename: Martin
authors.initials: M
authors.lastname: Widschwendter
authors.forename: Hella
authors.initials: H
authors.lastname: Lichtenberg-Fraté
authors.forename: Usha
authors.initials: U
authors.lastname: Menon
mesh_terms: D000368:Aged; D000735:Androstenedione / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004958:Estradiol / Q000097:blood; D047628:Estrogen Receptor alpha / Q000097:blood*; D047629:Estrogen Receptor beta / Q000097:blood*; D004970:Estrone / Q000097:blood; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood*; D006801:Humans; D007118:Immunoassay; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood*; D011944:Receptors, Androgen / Q000097:blood*; D018570:Risk Assessment; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000097:blood
chemical_list: C410798:AR protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012739:Gonadal Steroid Hormones; D011944:Receptors, Androgen; D012738:Sex Hormone-Binding Globulin; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate