Influence of treatment with onapristone on the IGF-system in breast cancer patients.
The influence of the novel antiprogestin onapristone on the serum insulin-like growth factor (IGF) system was studied in a group of 13 postmenopausal women with metastatic breast cancer. Blood samples were obtained before treatment and subsequently after 1, 2 and 3 months on therapy. IGF-I, IGF-II and IGF-binding protein (IGFBP)-2 were measured by radioimmunoassay (RIA). In addition, the IGFBP profile was evaluated by 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% increase over baseline at 3 months). There was a non-significant trend towards an initial decrease in IGFBP-3 fragmentation. No significant alterations 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 cortisol 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 progression as has been observed in patients suffering from prostatic cancer.
Helle
S I
SI
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Jonat
W
W
Giurescu
M
M
Ekse
D
D
Holly
J M
JM
Lønning
P E
PE
D000328:Adult; D000368:Aged; D000735:Androstenedione / Q000097:blood; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood* / Q000188:drug therapy; D005260:Female; D006067:Gonanes / Q000494:pharmacology* / Q000627:therapeutic use; D006727:Hormone Antagonists; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000737:chemistry; D018974:Insulin-Like Growth Factor Binding Protein 4 / Q000097:blood; D018969:Insulin-Like Growth Factor Binding Proteins / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017698:Postmenopause
D000970:Antineoplastic Agents; D006067:Gonanes; D006727:Hormone Antagonists; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D018974:Insulin-Like Growth Factor Binding Protein 4; D018969:Insulin-Like Growth Factor Binding Proteins; D000735:Androstenedione; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; C053238:onapristone; D006854:Hydrocortisone