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

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 IGF-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 IGF-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.