Postoperative Use of Zoledronic Acid in Breast Cancer Patients After Neoadjuvant Chemotherapy

Inclusion Criteria:

• Written informed consent must be obtained and documented according to the localregulatory requirements prior to beginning specific protocol procedures;

• Complete baseline documentation sent to GBG;

• Prior preoperative chemotherapy for at least 4 cycles, of which at least two mustcontain a taxane and an anthracycline;

• Completely resected unilateral or bilateral primary carcinoma of the breast withhistologically detectable tumor residuals (ypT1-4) and/or histology confirmedinvolvement of axillary nodes (ypN1-3). Sentinel node biopsy is allowed, but completeaxillary clearance is mandatory in node positive cases;

• A maximum interval of 3 years from date of axillary surgery to entering this trial;

• Age 18 years or older;

• Karnofsky index >= 70%;

• Life expectancy of at least 10 years, disregarding the diagnosis of cancer;

• No clinical evidence of local recurrence or distant metastases. Complete stagingwork-up: All patients must have breast ultrasound, chest X-ray, ultrasound or CT scanof the liver within 3 months prior to registration, as well as (bilateral) mammographyor breast MRI and bone scan within 8 months prior to registration. In case of apositive bone scan, bone X-ray is mandatory. Other tests may be performed asclinically indicated;

• Adequate renal and hepatic function (serum creatinine, bilirubin, and transaminaseswithin 1.5 × upper normal range);

• Patients must be available and compliant for treatment and follow-up. Patientsregistered on this trial must be treated and followed up at the participating center.

Exclusion Criteria:

• Known hypersensitivity reaction to the investigational compound;

• Prior postoperative chemotherapy;

• Prior treatment with bisphosphonates since breast cancer surgery;

• Pregnant or lactating patients. Patients of childbearing potential must have anegative pregnancy test (urine or serum) within 14 days prior to registration and mustimplement adequate non-hormonal contraceptive measures (barrier methods, intra uterinecontraceptive devices, sterilization) during study treatment;

• History of diseases with influence on bone metabolism, such as Paget's disease of boneand primary hyperparathyroidism or osteoporosis requiring treatment at the time ofstudy entry or considered likely to become necessary within the six months

• Other serious illness or medical condition that may interfere with the understandingand giving of informed consent and the conduct of the study

• Prior or concomitant secondary malignancy (except non-melanomatous skin cancer orcarcinoma in situ of the uterine cervix)

• Concurrent treatment with other experimental drugs or any other anti-cancer therapy;

• Abnormal renal function as evidenced by a calculated creatinine clearance < 30ml/minute;

• Serum calcium concentration < 8.0 mg/dl (2.00 mmol/L) or > 12.0 mg/dl (3.00 mmol/L)

• Concurrent treatment with sex hormones. Prior treatment must be stopped before studyentry;

• Current active dental problems including infection of the teeth or jawbone (maxilla ormandibular); dental or fixture trauma, or a current or prior diagnosis ofosteonecrosis of the jaw, of exposed bone in the mouth, or of slow healing afterdental procedures.

• Recent (within 6 weeks) or planned dental or jaw surgery (e.g.. extraction, implants)

• Male patients.