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‐binding proteins (IGFBPs). IGFBP‐3 is one such protein which either suppresses or enhances the actions of IGFs. Findings from most in vitro studies suggest that IGFBP‐3 inhibits breast cancer cell growth and facilitates apoptosis, but clinical studies have found that high levels of IGFBP‐3 in breast cancer tissues are associated with unfavourable prognostic indicators of the disease, such as large tumour size, low levels of steroid hormone receptors, elevated S‐phase fraction and DNA aneuploidy. To further examine the role of IGFBP‐3 in breast cancer recurrence and survival, we conducted the following nested case‐control study. From a cohort of 1,000 women treated surgically for primary breast cancer, we consecutively selected 100 patients who developed recurrent disease after surgery and 100 age‐ and year of diagnosis‐matched patients who had no relapse. Concentrations of IGFBP‐3 in breast tissue extracts were determined with an ELISA. Inverse correlations of IGFBP‐3 were revealed with estrogen receptor expression and patient age but not with tumour size or S‐phase fraction. Levels of IGFBP‐3 in breast tissues were slightly higher in the recurrent patients than in controls, but the differences were not statistically significant. No significant association was found between IGFBP‐3 and breast cancer recurrence. Survival analysis, however, indicated that the risk of death was increased 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 features of breast cancer. Int. J. Cancer (Pred. Oncol.) 79:624–628, 1998. © 1998 Wiley‐Liss, Inc.