Alterations in the insulin-like growth factor system during treatment withdiethylstilboestrol in patients with metastatic breast cancer

Alterations in the insulin-like growth factor (IGF)-system were evaluated i n 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 Weste rn ligand blotting as well as immunoblotting for IGFBP-3. We observed a sig nificant decrease (percentage of pretreatment levels with 95 confidence int ervals 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 7 1% (54-95); 1 month 78% (64-94); 2-3 months 71% (54-93)]. Contrary. the pla sma 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 s tudy confirms previous observations during treatment with oral oestrogens i n substitution doses, the reduction in plasma IGF-II, free IGF-I, IGFBP-2 a nd -3 are all novel findings. A profound decrease in free IGF-I suggests a reduced bioavailability of IGFs from plasma to the tissues. These observati ons may be of significance to understand the mechanisms of the antitumour e ffect of diethylstilboestrol in pharmacological doses. (C) 2001 Cancer Rese arch Campaign http://www.bjcancer.com.