A large, long-term study has found that the routine use of zoledronic acid in the adjuvant management of breast cancer is not beneficial, but might extend survival in a subset of postmenopausal women.

Data suggest that the adjuvant use of bisphosphonates reduces recurrence rates and death in patients with early-stage breast cancer. To determine whether the bisphosphonate zoledronic acid—mainly used in the treatment of osteoporosis—would improve disease outcomes in such patients, Robert E. Coleman, MB, BS, MD, of the University of Sheffield (Sheffield, United Kingdom) and colleagues initiated the Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE) trial.

A total of 3,360 patients with early-stage breast cancer were randomly assigned to receive standard adjuvant systemic therapy either with or without zoledronic acid. At a median follow up of 59 months, the investigators found no significant differences in the primary end point of disease-free survival between the two groups: the rate was 77% for each group. Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 in the control group, resulting in an overall survival rate of 85.4% in the zoledronic acid group and 83.1% in the control group.

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However, in women who had undergone menopause more than 5 years earlier, the 5-year overall survival rate was 84.6% in the zoledronic acid group and and 78.7% in the control group. In all other patients, this rate was 85.7% in the zoledronic acid group and 85.1% in the control group. These differences were independent of estrogen-receptor status, tumor stage, and lymph-node involvement.

A total of 17 confirmed and nine suspected cases of osteonecrosis of the jaw occurred in 17 zoledronic acid users; no cases were seen in the control group. Rates of other adverse effects were similar between the two groups.

Zoledronic acid was associated with a reduction in fracture rates, particularly among patients who had a disease recurrence.

Coleman and associates concluded in their report for The New England Journal of Medicine that the study results do not support the routine use of zoledronic acid as adjuvant therapy in unselected patients with early-stage breast cancer. But for postmenopausal women, the use of bisphosphonates remains appropriate for the prevention of treatment-induced bone loss and osteoporosis, and might have beneficial effects on disease outcomes (www.nejm.org/doi/pdf/10.1056/NEJMoa1105195).