Plasma insulin-like growth factor binding protein-3 proteolysis is increased in primary breast cancer

Pasting blood samples were obtained before definitive surgery or biopsy in 128 patients referred to the department of surgery with suspected or manife st breast cancer. Insulin-like growth factor (IGF)-I, IGF-II and free IGF-I were measured by radioimmunoassay/immunoradiometric assay, while IGFBP-3 p roteolysis was evaluated by Western immunoblot. 12 patients had ductal carc inoma in situ benign conditions, while staging revealed metastatic disease in 15 of 16 patients with invasive cancers. IGFBP-3 proteolysis above the n ormal range was recorded in 19 patients with invasive cancers, but in none of the patients suffering from DCIS/benign conditions. Increased IGFBP-3 pr oteolysis was most frequently recorded in patients harbouring large tumours and metastatic disease (Stage I: 0/19, 0%; Stage II: 3/45, 7%, Stage III: 9/37. 24%. and Stage IV: 7/15, 47%). IGFBP-3 proteolysis was significantly higher in Stage III (P = 0.01) and IV (P < 0.001) patients compared to the other stage groups (P = 0.001). IGF-I and IGF-II correlated negatively to I GFBP-3 proteolysis and age. Plasma levels of IGF-I and -II were significant ly lower in patients with elevated IGFBP-3 proteolysis compared to those wi thin the normal range. Our findings reveal alterations in the IGF-system am ong a substantial number of patients with large primary breast cancers. (C) 2001 Cancer Research Campaign http://www.bjcancer.com.