Background: Over 50% of breast cancer patients who relapse systemically develop bone metastases. The RANK/RANKL/OPG axis governs osteoclastogenesis and bone reabsorption. In particular, osteoprotegerin (OPG) is a decoy receptor of RANK-L (receptor activator of nuclear factor kappa B ligand) and seems to prevent bone destruction by blocking the binding of RANKL with its receptor. We studied the efficacy of circulating OPG compared to the traditional markers CEA and CA15-3 for the early detection of bone lesions.Methods: The study was carried out on peripheral blood from 72 patients with breast cancer, of whom 33 were disease-free and 39 had bone metastases. The OPG transcript was determined using quantitative PCR analysis, and the traditional markers were quantified by immunoenzymatic assays.Results: The OPG median value was higher in disease-free patients (median = 1.7, 0.4-8.9) than in bone-relapse patients (median = 0.6, 0.1-5.2) (p<0.001). CEA and CA15-3 median values were 1.3 (0.0-8.3) ng/ml and 10.6 (0-45.7) U/ml, respectively, in disease-free patients and 4.8 (0.0-90.6) ng/ml and 69.8 (7-1538) U/ml, respectively, in patients with bone metastases (p< 0.0001 for both markers). Considering 0.9 as cut off of OPG relative expression, our analyses revealed a specificity of 88% with respect to 97% for CEA and 94% for CA15-3. OPG sensitivity was 73% compared to only 49% for CEA and 67% for CA15-3. When OPG was considered in combination with the traditional markers, sensitivity increased from 49% to 83% for CEA and from 67% to 88% for CA15.3.Conclusions: Our results on a preliminary series of breast cancer patients indicate that the bone turnover marker OPG greatly increases CEA and CA15-3 sensitivity in predicting bone metastases.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3027.