Zoledronic acid and clodranate are the recommended bisphosphonates for the adjuvant treatment of patients with breast cancer, according to a clinical practice guideline issued by Cancer Care Ontario and the American Society of Clinical Oncology (ASCO).1

Cancer Care Ontario and ASCO convened a Working Group and Expert Panel to conduct a systematic review of the literature and develop evidence-based recommendations regarding the use of bisphosphonates and other bone-bone modifying agents as adjuvant therapy for patients with breast cancer.

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The joint Panel’s systematic review showed that adjuvant bisphosphonates reduce bone recurrence and prolong survival in postmenopausal women with nonmetastatic disease. In addition, the investigators found that absolute benefit is greater in patients who are at high risk for disease recurrence and most studies evaluated zoledronic acid or clodranate, with minimal data for other bisphosphonates. Denosumab reduced the rate of fractures, but its impact on long-term survival remains unclear.

Based on their findings, the Working Group and Expert Panel recommends that clinicians consider zoledronic acid or clodranate, if available, as adjuvant therapy for postmenopausal women with breast cancer eligible to receive adjuvant systemic therapy.

Specifically, the Panel recommends that patients who will receive adjuvant bisphosphonates should receive zoledronic acid at 4 mg intravenously over at least 15 minutes every 6 months for 3 to 5 years or clodranate at 1600 mg orally daily for 2 to 3 years; however, clinicians may consider different durations.

Prior to initiating adjuvant therapy with bisphosphonates, patients should undergo a dental assessment, where feasible, and manage any pending dental or oral problems, if possible. Clinicians should also inform patients of the risk of developing osteonecrosis of the jaw. The Panel also recommends calcium and vitamin D supplementation unless otherwise contraindicated. 

Although adjuvant denosumab appears promising, data at this time were insufficient for the Panel to recommend its use in the adjuvant setting. Head-to-head trials comparing denosumab with bisphosphonates and studies evaluating denosumab administration schedules should be conducted.


1. Dhesy-Thind S, Fletcher GG, Blanchette PS, et al. Use of adjuvant bisphosphonates and other bone-modifying agents in breast cancer: A Cancer Care Ontario and American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2017 March 6. doi: 10.1200/JCO.2016.70.7257 [Epub ahead of print]