ELEVATED PLASMA OSTEOPONTIN IN METASTATIC BREAST-CANCER ASSOCIATED WITH INCREASED TUMOR BURDEN AND DECREASED SURVIVAL

Osteopontin (OPN) is a secreted, integrin-binding phosphoprotein that has been implicated in both normal and pathological processes; qualita tive increases in OPN blood levels have been reported in a small numbe r of patients with metastatic tumors of various kinds, We measured pla sma OPN levels in 70 women with known metastatic breast carcinoma, 44 patient controls who were on follow-up after completion of adjuvant tr eatment for early breast cancer, and 35 normal volunteers. The median plasma OPN of patients with metastatic disease was 142 mu g/liter (ran ge, 38-1312 mu g/liter) and was significantly different (P < 0.0001, M ann Whitney U test) from both control groups (medians, 60 and 47 mu g/ liter; ranges, 15-117 and 22-122 mu g/liter), Furthermore, we found th at increasing plasma OPN is associated with shorter survival (P < 0.00 1) when patients were grouped in terciles for plasma OPN, This was als o demonstrated when using a Cox proportional hazards model, Median pla sma OPN levels were significantly increased for three or more sites of involvement (median, 232 mu g/liter; n = 13) versus 1 or 2 metastatic sites (medians, 129 and 130 mu g/liter; n = 29 and 28, respectively), Plasma OPN levels were correlated with other biochemical markers rela ted to the extent of disease, such as serum alkaline phosphatase, aspa rtate succinate aminotransaminase, and albumin (r = 0.81, 0.62, and -0 .56, respectively; all P < 0.001).