The role of CXCR4 in the prediction of bone metastases from breast cancer: A pilot study

Objective: The chemokine receptor CXCR4 is involved in tumor growth and homing of cancer cells to distant sites. The aim of our retrospective case-control study was to evaluate whether CXCR4 expression is more effective than conventional markers (estrogen receptor and HER-2) in predicting bone relapse in breast cancer. Methods: CXCR4 expression was evaluated by immunohistochemical staining in paraffin-embedded tissue sections of primary breast cancers from 20 patients with bone metastases (BM), 10 with visceral metastases (VM) and 10 with no evidence of disease (NED) at a median follow-up of 10.5 years (range 10.1-11.8). Results: Cytoplasmic CXCR4 expression was high in BM patients (45%, 95% CI 23-67), much lower in NED patients (10%, 95% CI 0-29) and negative in the VM group. CXCR4 coexpression in the nucleus and cytoplasm was observed in about half of the BM patients (45%) but never in NED or VM patients (p = 0.013). Conversely, estrogen receptor-positive and HER-2-negative status identified 80 and 95% of bone relapse patients, respectively, but did not discriminate between cases and controls. Conclusions: Our results suggest a pivotal role of CXCR4 expression as a predictor of BM in primary breast cancer. A larger study is ongoing to confirm these results.