title: The association between reproductive and hormonal factors and ovarian cancer by estrogen-α and progesterone receptor status.
abstract: OBJECTIVE
  We assessed the association between reproductive and hormonal factors and ovarian cancer incidence characterized by estrogen receptor-α (ERα) and progesterone receptor (PR) status.
  
  
  METHODS
  Tissue microarrays were used to assess ERα and PR expression among 197 Nurses' Health Study (NHS), 42 NHSII and 76 New England Case-Control Study (NECC) ovarian cancer cases. NHS/NHSII cases were matched to up to 4 controls (n=954) on diagnosis date and birth year. NECC controls (n=725) were frequency matched on age. Cases were considered receptor positive if ≥1% of tumor cells stained positive. Associations by ERα and PR status were assessed using polytomous logistic regression. p-Value for heterogeneity was calculated using a likelihood ratio test.
  
  
  RESULTS
  45% of ovarian tumors were PR(+), 78% were ERα(+) and 45% were ERα(+)/PR(+), while 22% were ERα(-)/PR(-). Postmenopausal status was associated with an increased risk of PR(-) tumors (OR: 2.07; 95%CI: 1.15-3.75; p-heterogeneity=0.01) and age at natural menopause was inversely associated with PR(-) tumors (OR, per 5years: 0.77; 95%CI: 0.61-0.96; p-het=0.01). Increasing duration of postmenopause was differentially associated by PR status (p-het=0.0009). Number of children and tubal ligation were more strongly associated with ERα(-) versus ERα(+) tumors (p-het=0.002 and 0.05, respectively). No differential associations were observed for oral contraceptive or hormone therapy use.
  
  
  CONCLUSIONS
  Postmenopausal women have an increased risk of developing PR(-) ovarian tumors compared to premenopausal women. The associations observed for ovarian cancer differ from those seen for breast cancer suggesting that the biology for tumor development through ERα and PR pathways may differ.
authors.affiliation: Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Ave, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA, USA. Electronic address: amy.shafrir@mail.harvard.edu.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Shafrir
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA, USA; Clinical and Translation Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, USA.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Rice
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA.
authors.forename: Mamta
authors.initials: M
authors.lastname: Gupta
authors.affiliation: Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Ave, Boston, MA, USA; Obstetrics and Gynecology Epidemiology Center, Department of Obstetrics and Gynecology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA, USA.
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Terry
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA, USA; Department of Biostatistics, Harvard TH Chan School of Public Health, 677 Huntington Ave, Boston, MA, USA.
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Rosner
authors.affiliation: Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Ave, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA, USA.
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, 330 Brookline Ave, Boston, MA, USA.
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Hecht
authors.affiliation: Department of Epidemiology, Harvard TH Chan School of Public Health, 677 Huntington Ave, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Ave, Boston, MA, USA.
authors.forename: Shelley S
authors.initials: SS
authors.lastname: Tworoger
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000328:Adult; D000367:Age Factors; D000368:Aged; D018269:Carcinoma, Endometrioid / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D015914:Estrogen Replacement Therapy / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D016015:Logistic Models; D008572:Menarche; D008593:Menopause; D008875:Middle Aged; D009367:Neoplasm Staging; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D010298:Parity; D017698:Postmenopause; D011980:Receptors, Progesterone / Q000378:metabolism*; D017584:Reproductive History; D013246:Sterilization, Tubal / Q000706:statistics & numerical data; D013997:Time Factors; D046888:Tissue Array Analysis; D014481:United States / Q000453:epidemiology
chemical_list: D003276:Contraceptives, Oral; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D011980:Receptors, Progesterone