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.