Influence of treatment with tamoxifen and change in tumor burden on the IGF-system in breast cancer patients.

Plasma levels of IGF-I, IGFBP-I and IGFBP-3 were measured before and during treatment with tamoxifen up to 19+ months in 34 post-menopausal patients with advanced breast cancer. In 28 patients, pro-IGF-IIE (IGF-IIE) levels were determined and IGFBP-3 was evaluated by immunoblot in 27 patients. Tamoxifen suppressed plasma levels of IGF-I by a mean value of 25.5%-37.7% at different times. This effect was fully developed after 1-2 months of treatment. IGF-IIE was decreased by a mean value of 7.7-23.2% at different time intervals during treatment with tamoxifen, but this effect was significant after long-term treatment (19 months +) only. Plasma IGFBP-I increased by a mean value varying between 48.6% and 190.1%. Tamoxifen had no significant effect on total IGFBP-3 levels. However, patients responding to treatment had a 28% reduction in fragmentation of IGFBP-3, while patients with progressive disease had a 36% increase in fragmentation. The difference between responders and non-responders was highly significant. These findings confirm and extend previous observations regarding the effects of treatment with tamoxifen on IGF-I and IGFBP-I. The finding that patients responding to tamoxifen achieve a reduction in the ratio of fragmented to intact IGFBP-3, while patients progressing on therapy experience an increase in the IGFBP-3 fragmentation ratio, suggest that the tumor burden influences IGFBP-3 protease activity in breast- cancer patients.