Influence of droloxifene on plasma levels of insulin-like growth factor (IGF)-I, Pro-IGF-IIE, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-3 in breast cancer patients

J Steroid Biochem Mol Biol. 1996 Feb;57(3-4):167-71. doi: 10.1016/0960-0760(95)00257-x.

Abstract

The influence of the novel anti-estrogen droloxifene on the insulin-like growth factor (IGF) system in plasma was studied in two groups of breast cancer patients receiving droloxifene 40 mg o.d. (group 1, n = 6) or 100 mg o.d. (group 2, n = 7). Fasting blood samples were obtained from all patients before treatment and after 3 months (group 1) or 6 months (group 2) on droloxifene treatment, except for two patients in group 2 from whom the second sample was obtained following 2 months on treatment when the drug was to be terminated due to progressive disease. Insulin-like growth factor (IGF)-I, insulin-like growth factor binding protein (IGFBP)-1, IGFBP-3 and pro-IGF-IIE (IGF-IIE) were measured by radioimmunoassay. In patients in group 1, plasma lGF-I levels decreased by a mean value of 20% (P < 0.05) on treatment with droloxifene, while IGFBP-1 increased by a mean value of 45% (P > 0.1). In group 2 we observed a 42% decrease in IGF-I during treatment (P < 0.025), while the level of IGFBP-1 increased by a mean value of 70% (P < 0.025). No significant effect on IGF-IIE or IGFBP-3 was noted in any of the groups. The change in plasma lGF-I and IGFBP-1 observed during treatment with droloxifene resembles what is found in patients treated with tamoxifen. As IGF-I is a potent mitogen for breast cancer cells in vitro, a decrease in the plasma level of this growth factor with an increase in the concentration of IGFBP-1 may contribute to the anti-tumour effects of droloxifene.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / drug therapy
  • Estrogen Antagonists / therapeutic use*
  • Humans
  • Insulin-Like Growth Factor Binding Protein 1 / blood
  • Insulin-Like Growth Factor Binding Protein 3 / blood
  • Insulin-Like Growth Factor Binding Proteins / blood*
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Middle Aged
  • Protein Precursors / metabolism
  • Somatomedins / metabolism*
  • Tamoxifen / analogs & derivatives*
  • Tamoxifen / therapeutic use

Substances

  • Antineoplastic Agents
  • Estrogen Antagonists
  • Insulin-Like Growth Factor Binding Protein 1
  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor Binding Proteins
  • Protein Precursors
  • Somatomedins
  • proinsulin-like growth factor II
  • Tamoxifen
  • droloxifene
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II