Several bisphosphonates including zoledronic acid (ZOL) are approved for treating bone metastases from breast cancer (BC). Recent trials demonstrated that ZOL prevents bone loss and reduces disease recurrence in early BC. This review uses pharmacodynamic, efficacy, and safety data from phase III trials of ZOL in early through metastatic BC to evaluate the dosing regimens used in each setting. The dosing frequencies of ZOL in early stage versus metastatic BC (4. mg 2-4 times per year versus monthly) are based on the respective levels of bone resorption and tumor burden. Data from ongoing clinical trials suggest that monthly dosing facilitates potential synergy between ZOL and chemotherapy in intermediate-risk BC and during neoadjuvant therapy. Overall, available data indicate that treatment with ZOL at appropriate intervals determined by disease characteristics helps attain key therapeutic goals in BC-maintaining skeletal integrity, reducing disease recurrence, and improving clinical outcomes.
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