e11507 Background: The RANK/RANK-L/OPG system is an important part of the bone metastasization process. CXCL12 is overexpressed in bone and like its receptor, CXCR4, is a determinant of organ tropism. The objective of the present study was to evaluate whether the expression of these markers in primary breast cancer can predict the onset of bone metastases. Methods: Marker expression was evaluated by immunohistochemical staining in paraffin-embedded sections of primary breast cancers from 40 individuals: 10 patients (median age 64 years, range 48-78) were disease-free (DFP) at a median of 9.8 (range 6.9-11.5) years, while 30 (median age 67 years, range 42-87) had relapsed. Within the latter subgroup, 10 (median age 66 years, range 42-87) had visceral metastases (VMP), and 20 (median age 69 years, range 42-87) had bone metastases (BMP). Results: In the overall series, 68% of tumors were ER-positive and 45% were PgR-positive. Moreover, 17.5% of tumors were positive for RANK, 22.5% for OPG and 25% for CXCR4. No significant associations were observed among the different markers. Analyzing the different patient subgroups, it was seen that RANK and OPG were equally expressed in 20% of DFP and in 25% of BMP. CXCR4 was expressed in only 10% of DFP but in 45% of BMP. Moreover, 20% of VMP expressed OPG but none showed RANK or CXCR4 expression. None of the patients expressed RANKL. The highest sensitivity in predicting bone metastasis was observed for ER positivity (80%), which, however, showed low specificity (30%), followed by triple positive RANK, CXCR4 and OPG (75%). Moreover, the highest specificity was observed for CXCR4 (90%) followed by RANK or OPG (80%). Conclusions: Our results indicate that, despite high sensitivity, ER-positive status is burdened by low specificity. Conversely, RANK, OPG, and CXCR4 expression would appear to be a more accurate predictor of bone relapse. The validation of these results is ongoing in a larger series of patients with breast cancer. No significant financial relationships to disclose.