Westbrook JA, et al. - In this investigation, researchers identified dedicator of cytokinesis protein 4 (DOCK4) as a potential biomarker for risk of bone metastasis development in patients with early breast cancer and assessed its utility in predicting response to adjuvant zoledronic acid (zoledronate). In a training tissue microarray with 345 patients who had early breast cancer, immunohistochemistry followed by Cox regression revealed that high DOCK4 expression correlated with histological grade, but not estrogen receptor status or lymph node involvement. A clinical validation TMA used tissue samples and the clinical database from the large AZURE adjuvant study. Adjusted Cox regression analyses demonstrated that high DOCK4 expression in the control arm (no zoledronate) was significantly prognostic for first recurrence in bone. There was no corresponding association in patients receiving zoledronate, suggesting that zoledronate treatment could counteract the increased risk of bone relapse from high DOCK4-expressing tumors. No association was found between high DOCK4 expression and metastasis to non-skeletal sites when these were evaluated collectively. Findings suggested that high DOCK4 was significantly linked to aggressive disease and future bone metastasis in early breast cancer and was possibly a valuable biomarker for subsequent bone metastasis risk.