title: Insulin-like growth factor-1, growth hormone, and daily cycling estrogen are associated with mammographic density in premenopausal women.
abstract: BACKGROUND
  Mammographic density represents epithelial and stromal proliferation, while insulin-like growth factor (IGF)-1, insulin-like growth factor-binding protein-3, growth hormone (GH), and estrogen may influence cellular proliferation. However, whether these growth factors independently, or in combination with estrogen, influence mammographic density in premenopausal women remains unclear.
  
  
  METHODS
  Growth factors were assessed in 202 ovulating premenopausal women participating in the Energy Balance and Breast Cancer Aspects-I study. Estrogen was assessed in serum, and daily in saliva, throughout a menstrual cycle. Computer-assisted mammographic density (Madena) was obtained from digitized mammograms (days 7-12 of the menstrual cycle). Associations between growth factors, estrogen, and mammographic density were studied in regression models.
  
  
  RESULTS
  Women with a mean age of 30.7 years had a mean percent mammographic density of 29.8%. Among women in the strata (above median split) of IGF-1 (>25 nmol/l) or GH (>0.80 mlU/l), we observed that an increase in salivary 17β-estradiol was associated with a higher odds for having higher percent mammographic density (>28.5%). The odds ratios (ORs) per standard deviation increase in 17β-estradiol were 1.81 [95% confidence interval (CI) 1.08-3.03] in the high IGF-1 stratum and 2.08 (95% CI 1.10-3.94) in the high GH stratum. Furthermore, women in these strata of growth factors (above median) who had an overall average 17β-estradiol above median (>16.8 pmol/l) had higher ORs for having higher percent mammographic density (>28.5%): IGF-1 4.13 (95 % CI 1.33-12.83) and GH 4.17 (95 % CI 1.41-12.28).
  
  
  CONCLUSIONS
  Growth factors, in combination with cycling estrogen, were associated with percent mammographic density, and may be of potential clinical relevance.
authors.affiliation: Department of Oncology, Oslo University Hospital HF, Ullevål, 0424, Oslo, Norway, hanne.frydenberg@medisin.uio.no.
authors.forename: Hanne
authors.initials: H
authors.lastname: Frydenberg
authors.forename: Vidar G
authors.initials: VG
authors.lastname: Flote
authors.forename: Anita
authors.initials: A
authors.lastname: Iversen
authors.forename: Sissi E
authors.initials: SE
authors.lastname: Finstad
authors.forename: Anne-Sofie
authors.initials: AS
authors.lastname: Furberg
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.forename: Tom
authors.initials: T
authors.lastname: Wilsgaard
authors.forename: Ellen
authors.initials: E
authors.lastname: Schlichting
authors.forename: Peter T
authors.initials: PT
authors.lastname: Ellison
authors.forename: Giske
authors.initials: G
authors.lastname: Ursin
authors.forename: Inger
authors.initials: I
authors.lastname: Thune
mesh_terms: D000328:Adult; D000071060:Breast Density; D001943:Breast Neoplasms; D004967:Estrogens / Q000032:analysis*; D005260:Female; D013006:Growth Hormone / Q000097:blood*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D042361:Mammary Glands, Human / Q000002:abnormalities*; D017697:Premenopause; D012463:Saliva / Q000737:chemistry
chemical_list: D004967:Estrogens; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone