Serum insulin-like growth factor-I and insulin-like growth factor binding protein-3 following chemotherapy for advanced breast cancer

Background: Insulin‐like growth factor‐I (IGF‐I) and IGF binding protein‐3 (IGFBP‐3) appear to influence the growth of breast cancer cells in vitro, and epidemiological studies suggest higher serum IGF‐I levels increase the risk of breast cancer. IGF‐I and IGFBP‐3 have therefore been measured in women with advanced breast cancer to determine if changes in serum levels predict the response to treatment by chemotherapy. Methods: Serum IGF‐I and IGFBP‐3 levels were measured in 14 patients before and after 1 week of chemotherapy. Changes in serum levels were compared with duration of survival. Results: Mean basal serum levels of IGF‐I and IGFBP‐3 were not significantly different between patients with advanced breast cancer and controls or women with early breast cancer. Serum IGFBP‐3 fell significantly 1 week after initiation of chemotherapy. Patient survival was not significantly related to baseline IGF‐I or IGFBP‐3 levels, but when the fall in serum levels 1 week after starting treatment was expressed either as absolute change or as a percentage of baseline, those individuals with a decrease in IGFBP‐3 greater than the median had significantly poorer survival (median survival 5.5 months vs 18 months). These results were independent of other prognostic variables such as previous disease‐free survival, and were also unaffected by the change in serum albumin with treatment. The fall in IGF‐I and IGFBP‐3 with chemotherapy mainly occurred in those with hepatic metastases, but prediction of survival was explained solely by the extent of the fall in IGFBP‐3. Conclusions: This preliminary study has shown that serum IGFBP‐3 falls significantly following initiation of chemotherapy and the extent of reduction significantly predicts the response to treatment.