Zometa and Circulating Vascular Endothelial Growth Factor (VEGF) in Breast Cancer Patients With Bone Metastasis

Inclusion Criteria: * Signed informed consent * Female, 18 years or older * Histologically confirmed invasive breast cancer * Bone metastases * ECOG Performance Status of 0 to 2 * Life expectancy of more than 3 months * Subject must have adequate organ function: * Cr ≤ 3 mg/dL (265 µmol/L)， * CrCl (Cockcroft \& Gault) ≥ 30 mL/min， * Ca2+ \> 8.0 mg/dL (2.0 mmol/L) and ≤ 12 mg/dL (3.0 mmol/L) * Negative serum pregnancy test for women with childbearing potential * Good conditions for infusion and willing to undergo phlebotomy during the whole study * Have ceased anti-tumor treatment including chemotherapy, endocrinotherapy and bio-targeted therapy for over 28 days Exclusion Criteria: * Pregnant or lactating females * History of other malignancy. However, subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible. * Concurrent disease or condition that would make the subject inappropriate for study participation, or any serious medical disorder that would interfere with the subject's safety * Active or uncontrolled infection * Current active dental problems including infection of the teeth or jawbone (maxilla or mandible); dental or fixture trauma; or a current or prior diagnosis of osteonecrosis of the jaw (ONJ); or exposed bone in the mouth; or slow healing after dental procedures * Recent (within 6 weeks of Randomization) or planned dental or jaw surgery (e.g. extraction, implants) * Known history of uncontrolled or symptomatic angina, arrhythmias, or congestive heart failure * Concomitant with liver, brain or symptomatic lung metastases (symptoms such as hemoptysis, severe cough and shortness of breath) * Accepted radiotherapy for solitary bone disease within 30 days before study * Previous treatment with other bisphosphonates or radionuclides within one month before study * Known hypersensitivity to bisphosphonates * History of treatment with calcitonin, gallium nitrate or mithracin within 14 days before study.