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Review: Adjuvant bisphosphonates in endocrine-responsive breast cancer: what is their place in therapy?

Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria, michael.gnant{at}meduniwien.ac.at

Peter Blaha

Department of Surgery, Medical University of Vienna, Vienna, Austria

Peter Dubsky

Department of Surgery, Medical University of Vienna, Vienna, Austria

Ruth Exner

Department of Surgery, Medical University of Vienna, Vienna, Austria

Florian Fitzal

Department of Surgery, Medical University of Vienna, Vienna, Austria

Emanuel Sporn

Department of Surgery, Medical University of Vienna, Vienna, Austria

Peter Panhofer

Department of Surgery, Medical University of Vienna, Vienna, Austria

Andrea Dal Borgo

Department of Surgery, Medical University of Vienna, Vienna, Austria

Sinda Bigenzahn

Department of Surgery, Medical University of Vienna, Vienna, Austria

Guenther Steger

Guenther Steger Department of Medicine I, Medical University of Vienna, Vienna, Austria

Raimund Jakesz

Department of Surgery, Medical University of Vienna, Währinger Gürtel 18-20, A-1090, Vienna, Austria michael.gnant@ meduniwien.ac.at

Recent advances in the treatment of early breast cancer have improved clinical outcomes and prolonged survival, especially in women with endocrine-responsive disease. However, cancer therapies including cytotoxic chemotherapy, ovarian suppression, and aromatase inhibitors can drastically reduce circulating estrogen, increasing bone loss and fracture risk. Because most women with early breast cancer will live for many years, it is important to protect bone health during cancer therapy. Several recent clinical trials combining adjuvant endocrine therapy with bisphosphonates have demonstrated efficacy for preventing cancer treatment-induced bone loss in pre- and postmenopausal women with early breast cancer. The largest body of evidence supporting the use of adjuvant bisphosphonates comes from studies with zoledronic acid; however, studies with risedronate, ibandronate, and denosumab (a biologic agent) have also demonstrated efficacy for preventing bone loss. Adding zoledronic acid to endocrine therapy prevents bone loss and improves bone mineral density (BMD). In addition, preclinical studies suggest that bisphosphonates have direct and indirect antitumor activity, such as inducing tumor cell apoptosis, reducing tumor cell adhesion and invasion, reducing angiogenesis, activating immune responses, and synergy with chemotherapy agents, among others. Clinical trials have demonstrated significantly improved disease-free survival in patients receiving adjuvant endocrine therapy plus zoledronic acid compared with endocrine therapy alone. Ongoing studies will further define the role of adjuvant bisphosphonates in maintaining bone health and improving clinical outcomes. The available evidence suggests that pre- and postmenopausal patients may receive clinical benefit from including bisphosphonates as part of their adjuvant treatment regimen for endocrine-responsive early breast cancer.

Key Words: adjuvant • antitumor • bisphosphonates • bone loss • breast cancer • disease recurrence • endocrine responsive • zoledronic acid

This version was published on November 1, 2009

Therapeutic Advances in Medical Oncology, Vol. 1, No. 3, 123-136 (2009)
DOI: 10.1177/1758834009344594


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