title: Prospective multicenter cohort study of estrogen and insulin-like growth factor system in BRCA mutation carriers.
abstract: OBJECTIVE
  Major clinical characteristics of BRCA1/2-related cancers include association with estrogen and metabolic consequences. We aimed to evaluate serum estradiol (E2) and insulin-like growth factor 1 (IGF-1) levels as a marker of insulin resistance in BRCA1/2 mutation carriers and high-risk, BRCA-negative controls.
  
  
  METHODS
  Eligible cancer-free women (age 18-42 with regular menstrual cycles) who had been screened for BRCA1/2 mutations between 2005 and 2013 completed a questionnaire and underwent a single blood draw. E2 was measured with radioimmunoassay, and IGF-1 was measured with enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Eighty-six women participated (44 carriers and 42 non-carriers) in this study. BRCA mutation carriers were significantly younger than non-carriers (p = 0.0002). Age-adjusted basal (menstrual cycle days 2-5) serum E2 level was not significantly different between BRCA mutation carriers and non-carriers (30.4 vs. 24.7 pg/mL, p = 0.07). BRCA mutation carriers have significantly lower age-adjusted serum IGF-1 levels compared to non-carriers (89.7 vs. 112.6 ng/mL, p < 0.001). In women with BRCA mutations, the risk of having low serum IGF-1 level (IGF-1: ≤85 ng/mL) was 10.7 times as great as that of women without BRCA mutations (95 % CI 2.5, 46.2). There was a significant inverse association between basal E2 and IGF-1 levels in BRCA mutation carriers after adjusting age and BMI (p = 0.03).
  
  
  CONCLUSIONS
  IGF-1 level is significantly lower in cancer-free BRCA mutation carriers versus BRCA-negative controls, and there is a potential association between E2 and IGF-1 in cancer-free BRCA mutation carriers. Our findings may instigate future studies evaluating the role of both E2 and IGF-1 in BRCA mutation carriers.
authors.affiliation: Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of North Carolina at Chapel Hill, 4001 Old Clinic Building, CB 7570, Chapel Hill, NC, 27599-7570, USA, dr.jykim76@gmail.com.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Johnson
authors.forename: C
authors.initials: C
authors.lastname: Skrzynia
authors.forename: A
authors.initials: A
authors.lastname: Buchanan
authors.forename: C
authors.initials: C
authors.lastname: Gracia
authors.forename: J E
authors.initials: JE
authors.lastname: Mersereau
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D004958:Estradiol / Q000097:blood*; D004967:Estrogens / Q000097:blood; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D009154:Mutation; D011446:Prospective Studies
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D004967:Estrogens; D004958:Estradiol; D007334:Insulin-Like Growth Factor I