The insulin-like growth factor (IGF)-system was evaluated in 150 breast cancer patients participating in a randomised phase III trial comparing octreotide pamoate and tamoxifen with tamoxifen + placebo. Alterations in the IGF-system in the two treatment arms and individual changes with respect to outcome were compared. Serum IGF-I and -II, free IGF-I and insulin-like growth factor binding protein 1-3 (IGFBP 1-3) were measured by radioimmmunoassay (RIA)/immunoradiometric assay (IRMA) and IGFBPs by Western ligand blots (WLB) before and during treatment. Combined treatment caused a higher increase in IGFBP-I and larger suppression of total and free IGF-I, IGF-II, and IGFBP-3 (P < 0.01 for all), but less suppression of IGFBP-2 (P < 0.05) compared with tamoxifen monotherapy. An increase in IGFBP-2 >= 25% was associated with decreased progression-free survival (PFS) in the total patient population and combined treatment group. Similar response rates and time to progression in the treatment arms suggests moderate suppression of circulating IGF-I has no influence on clinical outcome. (c) 2005 Elsevier Ltd. All rights reserved.