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Recommendations for use of Bisphosphonates

Summary of evidence

The NBOCC* statements and recommendations about the use of bisphosphonates for women with advanced breast cancer are based on a Cochrane review and meta-analysis investigating the use of bisphosphonates for breast cancer (2005 and 2007 update)2 and an NBOCC* systematic review,3 which includes available evidence published between January 2007 and April 2010 from randomised trials.

The Cochrane review includes 18 published randomised controlled trials, which examined the effect of bisphosphonates in women with advanced breast cancer. The studies compared the use of any bisphosphonate administered orally or intravenously in any dose and for any duration with placebo, no treatment or another bisphosphonate. The majority (15 studies) included women with advanced breast cancer and clinically evident bone metastases (metastases confirmed with diagnostic imaging). Three studies included women without clinically evident bone metastases with locally advanced or advanced breast cancer.

Eleven studies investigated oral ibandronate, clodronate or pamidronate administered either daily or twice a day. Seven studies investigated intravenous pamidronate, ibandronate, clodronate or zoledronic acid, given every three to four weeks. Most studies administered bisphosphonates for a duration between one and two years.

Bisphosphonates were administered in addition to other systemic therapies, such as chemotherapy or hormonal therapy. Since the studies included in the Cochrane review were published between 1983 and 2004, the concurrent systemic therapies used in these studies may differ from the current standard breast cancer treatments (such as aromatase inhibitors, taxanes and targeted therapies).

The NBOCC* systematic review identified one meta-analysis on the effect of oral clodronate for breast cancer, five full text papers describing randomised trials of bisphosphonates for advanced breast cancer and one additional study reported in abstract only. All studies identified were in women with breast cancer with bone metastases. Various bisphosphonate comparisons were investigated, as well as a comparison with subcutaneous denosumab, a new bone agent.

(See Table 1 Meta-analysis results of study outcomes from the Cochrane Review)

* In July 2011, National Breast and Ovarian Cancer Centre (NBOCC) amalgamated with Cancer Australia to form a single national agency, Cancer Australia, to provide leadership in cancer control and improve outcomes for Australians affected by cancer.

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