Potential usefulness of OPG, a member of the tumor necrosis factor receptor superfamily, for the early diagnosis of bone metastasis in breast cancer patients

Abstract

e22000 Background: Breast cancer is the most frequent tumor in women. About 80% of patients with metastatic disease present bone involvement, in which the OPG/RANKL/RANK system would seem to play an important role. Our aim was to evaluate the potential usefulness of OPG bone marker for the early diagnosis of bone metastases. Methods: The study was carried out on 120 individuals: 30 healthy donors, with a median age of 40 years (21–76) and 90 breast cancer patients, with a median age of 57 years (30–86). Among patients, 49 were disease-free (median age 52 years) and 41 were at first diagnosis of bone metastases (median age 63 years). OPG transcript was determined in peripheral blood samples using quantitative PCR analysis. A receiver operating characteristic (ROC) curve was used to calculate the diagnostic accuracy of the marker. Results: OPG values were not correlated with age in any of the subgroups. The OPG median value was not statistically different in healthy donors (median=1.9; range 0.6–4.7) and disease-free patients (median=1.7; range 0.4–8.9), whereas it was threefold higher than that observed in relapsed patients (median=0.6; range 0.1–5.2; p<0.001), regardless of the number of metastatic sites. The area under the curve (AUC) in disease-free patients was 0.82 for OPG, with 71% sensitivity and 88% specificity, using a cut off ≤ 0.8. In a parallel analysis of 37 patients (14 disease-free and 23 with bone metastases) for whom CEA and CA15.3 information was available, specificity for each marker was 100%, whereas sensitivity was only 61% and 59%, respectively. When these markers were considered in combination with OPG, an increase in sensitivity, albeit not statistically significant, was observed for CEA (83%) and CA15.3 (82%). Conclusions: Our preliminary data show a potential role of the OPG bone turnover marker for the early diagnosis of bone metastases. Results now need to be confirmed in a larger case series. No significant financial relationships to disclose.