Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer

Int J Cancer. 1995 Jul 28;62(3):266-70. doi: 10.1002/ijc.2910620306.


Insulin-like growth factor I (IGF-I) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-I is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-I for biological activity. To assess the availability of IGF-I for receptor binding, we determined serum levels of IGF-I and IGFBP-3 and IGF-I/IGFBP-3 ratios. In a case-control study, 150 women aged 38 to 75 years presenting with stage-I or -II breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-I serum concentrations, decreased IGFBP-3 levels and increased IGF-I/IGFBP-3 ratios. The IGF-I/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-I/IGFBP-3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF-I in the circulation of pre-menopausal women may contribute to the development of breast cancer.

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / blood*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / surgery
  • Carrier Proteins / blood*
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Premenopause / blood*
  • Reference Values
  • Risk Factors


  • Carrier Proteins
  • Insulin-Like Growth Factor Binding Proteins
  • Insulin-Like Growth Factor I