title: Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women.
abstract: BACKGROUND
  Studies have shown a positive association between serum insulin-like growth factor (IGF)-I and breast cancer risk in premenopausal but not postmenopausal women. IGF-II and estrogen receptor (ER) status has never been investigated. We examined the association between IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and IGFBP-3 protease activity and breast cancer risk in postmenopausal women, taking ER status of the breast cancer into consideration.
  
  
  METHODS
  We conducted this case-cohort study within a Danish follow-up study based on 24,697 postmenopausal women. We identified 411 cases with breast cancer and a matched control group including 397 cohort members. We estimated breast cancer risk using Cox regression analysis with adjustment for known breast cancer risk factors.
  
  
  RESULTS
  We observed no association for IGF-I but a positive association between levels of IGFBP-3 and breast cancer risk. Per 500 units higher levels of IGFBP-3, an incidence rate ratio [IRR; 95% confidence interval (95% CI)] of 1.14 (1.00-1.30) was estimated. For ER-positive breast cancer, the IRR (95% CI) was 1.18 (1.05-1.33). IGFBP-3 protease activity was not associated with breast cancer risk. Per 275 units higher levels of IGF-II, an IRR (95% CI) of 1.35 (1.10-1.66) was observed for ER-positive tumors, whereas IGFBP-2 was not associated with breast cancer risk. Adjustment for potential confounders did not change the risk estimate. There was no association between IGF-I, IGF-II, IGFBP-2, or IGFBP-3 and risk of ER-negative breast cancer.
  
  
  CONCLUSIONS
  Serum IGFBP-3 and IGF-II levels were positively associated with ER-positive breast cancer risk. This may suggest an important relationship among IGFs, IGFBPs, the ER system, and breast cancer development in postmenopausal women.
authors.affiliation: Medical Department V, Aarhus Kommunehospital, Norrebrogade 44, DK-8000 Aarhus C, Denmark. henning.gronbaek@dadlnet.dk
authors.forename: Henning
authors.initials: H
authors.lastname: Grønbaek
authors.forename: Allan
authors.initials: A
authors.lastname: Flyvbjerg
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjaer
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Jane
authors.initials: J
authors.lastname: Christensen
authors.forename: Henrik Toft
authors.initials: HT
authors.lastname: Sørensen
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
mesh_terms: D001943:Breast Neoplasms; D016022:Case-Control Studies; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D016015:Logistic Models; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D017698:Postmenopause / Q000097:blood*; D012042:Registries; D012307:Risk Factors; D013002:Somatomedins / Q000378:metabolism*
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins