INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-3 AND BREAST-CANCER SURVIVAL

Insulin-like growth factors (IGFs) are potent mitogens involved in the regulation of cell proliferation and apoptosis. The action of IGFs is mediated through a specific cell membrane receptor (IGF-IR), and the interactions between IGFs and this receptor are regulated by IGF-bindi ng proteins (IGFBPs). IGFBP-3 is one such protein which either suppres ses or enhances the actions of IGFs. Findings from most in vitro studi es suggest that IGFBP-3 inhibits breast cancer cell growth and facilit ates apoptosis, but clinical studies have found that high levels of IG FBP-3 in breast cancer tissues are associated with unfavourable progno stic indicators of the disease, such as large tumour size, low levels of steroid hormone receptors, elevated S-phase fraction and DNA aneupl oidy. To further examine the role of IGFBP-3 in breast cancer recurren ce and survival, we conducted the following nested case-control study. From a cohort of 1,000 women treated surgically for primary breast ca ncer, we consecutively selected inn patients who developed recurrent d isease after surgery and 100 age- and year of diagnosis-matched patien ts who had no relapse. Concentrations of IGFBP-3 in breast tissue extr acts were determined with an ELISA. Inverse correlations of IGFBP-3 we re revealed with estrogen receptor expression and patient age but not with tumour size or S-phase fraction. Levels of IGFBP-3 in breast tiss ues were slightly higher in the recurrent patients than in controls, b ut the differences were not statistically significant. No significant association was found between IGFBP-3 and breast cancer recurrence. Su rvival analysis, however, indicated that the risk of death was increas ed with higher IGFBP-3 levels, and the association was independent of other prognostic markers. In conclusion, our results demonstrate that high levels of IGFBP-3 are associated with unfavourable prognostic fea tures of breast cancer. (C) 1998 Wiley-Liss, Inc.