There is clear preclinical in vitro and in vivo evidence of sequence dependent synergy between chemotherapy agents and zoledronic acid. The aim of the study is to investigate if the synergistic increase in tumour cell apoptosis observed in preclinical studies occurs in patients. The hypothesis for this study is that there may be anti-tumour benefits of the sequential application of chemotherapy agents followed by zoledronic acid in patients with invasive breast cancer.

Inclusion Criteria:

• Women with histological diagnosis of invasive breast cancer requiring neoadjuvant chemotherapy
• T2 tumour or above
• WHO Performance status of 0,1 or 2
• Must consent to or have undergone a core biopsy for diagnosis of breast cancer AND consent to undergo an additional core biopsy prior to the second cycle of chemotherapy (Day 5 +/- Day 21)
• Written informed consent

Exclusion Criteria:

• Previous chemotherapy or radiotherapy to treated breast
• Evidence of metastatic disease or recurrent breast cancer or previous malignancy (some exceptions)
• Calculated creatinine clearance < 40mls/min
• Prior treatment with bisphosphonates in last year or known contraindications to bisphosphonate therapy
• Concurrent tamoxifen or aromatase inhibitor medication
• Pregnant or lactating women
• Cardiac dysfunction that precludes use of anthracycline chemotherapy
• Unwilling to have extra interim biopsy