Alterations in the insulin-like growth factor system during treatment with diethylstilboestrol in patients with metastatic breast cancer.
Alterations in the insulin-like growth factor (IGF)-system were evaluated in 16 patients treated with diethylstilboestrol 5 mg 3 times daily. Fasting blood samples were obtained before treatment and after 2 weeks, 1 month and/or 2-3 months on therapy. Insulin-like growth factor (IGF)-I, IGF-II, free IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-2 and IGFBP-3 were measured by radioimmuno-/immunoradiometric-assays. All samples were subjected to Western ligand blotting as well as immunoblotting for IGFBP-3. We observed a significant decrease (percentage of pretreatment levels with 95 confidence intervals of the mean) in IGF-I [2 weeks 63% (49-79); 1 month 56% (44-73); 2-3 months 66% (53-82)], IGF-II [2 weeks 67% (56-80); 1 month 60% (52-68); 2-3 months 64% (55-75)], free IGF-I [2 weeks 29% (19-42); 1 month 25% (18-36); 2-3 months 31% (21-46)], IGFBP-2 [2 weeks 53% (18-156); 1 month 69% (61-78); 2-3 months 66% (57-78)], IGFBP-3 [2 weeks 74% (63-85); 1 month 69% (62-76); 2-3 months 71% (63-80)], as well as IGFBP-3 protease activity [2 weeks 71% (54-95); 1 month 78% (64-94); 2-3 months 71% (54-93)]. Contrary, the plasma levels (percentage of pretreatment levels with 95 confidence intervals of the mean) of IGFBP-1 [2 weeks 250% (127-495); 1 month 173% (138-542); 2-3 months 273% (146-510)] and IGFBP-4 [2 weeks 146% (112-192); 1 month 140% (116-169); 2-3 months 150% (114-198)] increased significantly. While this study confirms previous observations during treatment with oral oestrogens in substitution doses, the reduction in plasma IGF-II, free IGF-I, IGFBP-2 and -3 are all novel findings. A profound decrease in free IGF-I suggests a reduced bioavailability of IGFs from plasma to the tissues. These observations may be of significance to understand the mechanisms of the antitumour effect of diethylstilboestrol in pharmacological doses.
Helle
S I
SI
Department of Oncology, Haukeland University Hospital, Bergen, N-5021, Norway.
Geisler
J
J
Anker
G B
GB
Leirvaag
B
B
Holly
J M
JM
Lønning
P E
PE
D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D004054:Diethylstilbestrol / Q000627:therapeutic use*; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007335:Insulin-Like Growth Factor II / Q000378:metabolism*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011863:Radioimmunoassay
D018931:Antineoplastic Agents, Hormonal; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D004054:Diethylstilbestrol