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Targeted therapies

Adjuvant bisphosphonates—an option with low estrogen?

Nature Reviews Clinical Oncology volume 8, pages 698–699 (2011)Cite this article

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The AZURE trial data add to the uncertainty of whether adjuvant bisphophonates are a valuable addition to the armamentarium in the treatment of early stage breast cancer. Although the overall trial results were negative, a prespecified subgroup analysis demonstrated a 25% reduction in the risk of relapse and death in postmenopausal patients.

The long-awaited results of the AZURE (Adjuvant Zoledronic Acid to Reduce Recurrence) trial were recently published.1 In this open-label phase III study, 3,360 patients with stage II or III breast cancer were randomly assigned to receive standard adjuvant systemic therapy (chemotherapy, endocrine therapy, immunotherapy, or a combination of these therapies) either with or without the addition of zoledronic acid. The aminobisphosphonate was administered every 3 to 4 weeks for six doses and then every 3 to 6 months for a duration of 5 years. Disease-free survival (DFS) was the primary trial end point, and after 59 months of follow up, there was no significant difference between the two cohorts in the overall analysis. Interestingly, a prespecified subgroup analysis demonstrated huge and unexpected heterogeneity (X2 = 7.91; P = 0.005) of the treatment effect with respect to the menopausal status of patients: although there was no significant difference between patients receiving zoledronic acid and those who did not in premenopausal and perimenopausal women, adjuvant bisphosphonate treatment resulted in notable 5-year DFS benefits (71% versus 78.2%; hazard ratio [HR] = 0.75; P = 0.02) and 5-year overall survival benefits (78.7% versus 84.6%; HR = 0.74; P = 0.04) in postmenopausal patients.1

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Figure 1: Hazard ratios of DFS in the AZURE postmenopausal subgroup and ABCSG-12 overall trial population.1,2

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  1. Department of Surgery and Comprehensive Cancer Center, Medical University of Vienna, Währinger Gürtel 18–20, Vienna, A-1090, Austria

    Michael Gnant

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Competing interests

M. Gnant has received research support from and has served as a consultant for AstraZeneca, Novartis, and Pfizer, and has received lecture fees and honoraria for participation on advisory boards from Amgen, AstraZeneca, Novartis, Pfizer, Roche, Sanofi-Aventis and Schering.

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Gnant, M. Adjuvant bisphosphonates—an option with low estrogen?. Nat Rev Clin Oncol 8, 698–699 (2011). https://doi.org/10.1038/nrclinonc.2011.170

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