Wilson C, et al. - This study represents the largest data collection of fracture incidence during adjuvant bisphosphonate use in breast cancer. The impact of adjuvant zoledronic acid (ZOL) on fractures was assessed in the AZURE trial, wherein, patients with stage II/III early breast cancer were administered ZOL 4 mg added to standard neo/adjuvant chemotherapy and/or endocrine therapy (control) for 5 years. An attenuation in the risk of clinical fractures was noted with adjuvant ZOL, the majority of this protection occurred after disease recurrence.

• In the AZURE trial, which represents an academic, multi-centre, randomised phase III study, the addition of ZOL 4 mg to standard therapy (neo/adjuvant chemotherapy and/or endocrine therapy) for 5 years (administered by intravenous (iv) infusion every 3–4 weeks for 6 doses, then 3 monthly × 8 and 6 monthly × 5) in patients with stage II/III early breast cancer was assessed.
• Following a median of 84.2 months of follow-up and 966 disease-free survival (DFS) events, fracture data collected as part of skeletal-related adverse event reporting were analyzed.
• Researchers evaluated number of fractures, time-to-first fracture and the incidence of fractures before and after disease recurrence.

• Data showed a total of 244 patients reported ≥1 fracture, 140 (8.3%) in the control arm (171 fractures) and 104 (6.2%) in the ZOL arm (120 fractures).
• Researchers observed that out of the 291 fractures reported, 207 fractures occurred in the absence of recurrence (control 111, ZOL 96), 80 after recurrence (control 59, ZOL 21).
• With ZOL, a reduction was noted in the 5-year fracture rate from 5.9% (95%CI 4.8, 7.1%; control) to 3.8% (95%CI 2.9, 4.7%).
• With ZOL, time-to-first fracture was significantly increased (HR 0.69, 95%CI 0.53–0.90; P=0.0053) but the majority of fracture prevention benefit occurred after a DFS event (HR 0.3; 95%CI 0.17, 0.53; P < 0.001).
• When observed across menopausal sub-groups, fracture benefits from ZOL were similar.