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Highlights • Questions around optimal use of bone-modifying agents (BMAs) still exist. • Most physicians are de-escalating BMAs in patients with metastatic breast cancer. • Practice varies according to patient insurance coverage. • There is interest performing further trials of de-escalation especially after 2 years of treatment., Background There remain questions around the optimal use of bone-modifying agents (BMAs) in patients with bone metastases from breast and castration-resistant prostate cancer (CRPC). A physician survey was performed to identify current practices, as well as perceptions around long-term BMA use, BMA de-escalation, and further BMA de-escalation after 2 years of use. Methods Canadian oncologists treating breast cancer or CRPC were surveyed via an anonymized online survey. The survey collected physician demographics, current practice patterns, perception on risk of symptomatic skeletal events (SSE) and BMA-associated toxicities, and attitudes towards further de-escalation of BMAs after 2 years of treatment. Results A total of 334 physicians in Canada were contacted, of which 295 were eligible on initial screening, and 65 completed the survey (response rate 22%): 35 treated breast cancer, 25 treated prostate cancer and 5 treated both. The most common BMA regimens in patients with no limitation in drug coverage were denosumab q4wks for 3–4 months followed by a de-escalation to q12wks (breast cancer) and denosumab q4wks (prostate cancer). In patients with provincial health coverage only the common choices were zoledronate q4wks for 3–4 months followed by de-escalation to q12wks (breast cancer) and denosumab q4wks (prostate cancer). There was equipoise regarding the benefit of continuing BMA beyond 2 years and interest in further trials of de-escalation of BMA in both breast and prostate cancer. The most favored alternative primary study endpoints to SSE were BMA toxicity (67.2%), pain (46.9%), and physical function (48.4%). Conclusion Despite their extensive use and costs, questions around optimal use of BMAs still exist. Practice varies according to patient insurance coverage. However, most physicians are de-escalating BMAs. There is interest amongst clinicians in performing trials of de-escalation, especially after 2 years of treatment.

Bone loss is common in patients with breast cancer. Bone modifying agents (BMAs), such as bisphosphonates and denosumab, have been shown to reverse or stabilize bone loss and may be useful in the primary and metastatic settings. The purpose of this review is to provide clear evidence-based strategies for the management of bone loss and its symptoms in breast cancer. A systematic review of clinical trials and meta-analyses published between 1996 and 2012 was conducted of MEDLINE and EMBASE. Reference lists were hand-searched for additional publications. Recommendations were developed based on the best available evidence. Zoledronate, pamidronate, clodronate, and denosumab are recommended for metastatic breast cancer patients; however, no one agent can be recommended over another. Zoledronate or any oral bisphosphonate and denosumab should be considered in primary breast cancer patients who are postmenopausal on aromatase inhibitor therapy and have a high risk of fracture and/or a low bone mineral density and in premenopausal primary breast cancer patients who become amenorrheic after therapy. No one agent can be recommended over another. BMAs are not currently recommended as adjuvant therapy in primary breast cancer for the purpose of improving survival, although a major Early Breast Cancer Cooperative Trialists’ Group meta-analysis is underway which may impact future practice. Adverse events can be managed with appropriate supportive care.