INFLUENCE OF TREATMENT WITH ONAPRISTONE ON THE IGF-SYSTEM IN BREAST-CANCER PATIENTS

The influence of the novel antiprogestin onapristone on the serum insu lin-like growth factor (IGF) system was studied in a group of 13 postm enopausal women with metastatic breast cancer. Blood samples were obta ined before treatment and subsequently after 1, 2 and 3 months on ther apy. IGF-I, IGF-II and IGF-binding protein (IGFBP)-2 were measured by radioimmunoassay (RIA). In addition, the IGFBP profile was evaluated b y Western ligand blotting (WLB), and IGFBP-3 fragmentation determined by immunoblotting. A moderate (29%) but significant increase in IGF-I was observed after 3 months on treatment (p < 0.05). IGFBP-2 showed a significant, progressive increase during treatment when evaluated both by WLB (44% increase over baseline at 3 months) and by RIA (33% incre ase over baseline at 3 months). There was a non-significant trend towa rds an initial decrease in IGFBP-3 fragmentation. No significant alter ations were observed in IGF-II or any of the binding proteins (except IGFBP-2) determined by Western ligand blotting. Due to the observation that onapristone treatment caused a moderate suppression of serum cor tisol and androstenedione, we postulate the observed increase in IGF-I to be due to a slight glucocorticoid agonistic effect of the drug. On the contrary, the increase in IGFBP-2 may be related to disease progr ession as has been observed in patients suffering from prostatic cance r. (C) 1998 Elsevier Science Ltd. AU rights reserved.