The statements and clinical practice recommendations about the use of bisphosphonates for women with early breast cancer are based on a Cancer Australia systematic review and meta-analysis (including available evidence published between 1 January 2007 and 18 August 2010)32 and a Cochrane review and meta-analysis investigating the use of bisphosphonates for breast cancer (2005 and 2007 update).20 Outcomes assessed include bone health, overall survival, cancer recurrence and metastases, quality of life and adverse events.
The Cochrane review and meta-analysis20 included three trials on the effect of oral clodronate in women with early breast cancer on survival and metastasis compared to placebo or open control. Updated follow-up data from two trials identified in the Cochrane review were included in the Cancer Australia systematic review.
The Cancer Australia systematic review identified four systematic reviews and 13 published randomised controlled trials, which examined the effects of bisphosphonates for women with early breast cancer. The quality of all systematic reviews and randomised controlled trials was rated fair to good. The four systematic reviews assessed: the effect of oral clodronate on survival (Ha 200733), the relationship between bisphosphonates and osteonecrosis of the jaw (Mauri 200931), the impact of bisphosphonates on disease course (Mauri 201034), and the impact of bisphosphonates on fracture prevention (Valachis 201019).
Ten of the randomised controlled trials identified in the Cancer Australia systematic review compared bisphosphonates to placebo or no bisphosphonate: three oral clodronate trials, one oral ibandronate trial, one oral pamidronate trial, three oral risedronate trials and two intravenous zoledronic acid trials. The remaining three randomised controlled trials compared upfronta intravenous zoledronic acid with delayedb delivery.
For all trials, bisphosphonates were administered in addition to standard adjuvant treatment, such as chemotherapy, endocrine therapy and radiotherapy.
Meta-analyses were conducted using the results from earlier systematic reviews20,34 and the subsequently published randomised controlled trials identified in the Cancer Australia systematic review to analyse the effect of bisphosphonates on overall survival, cancer recurrence, metastasis, and incidence of osteoporosis and fracture.
a The upfront groups received intravenous zoledronic acid immediately after random assignment
b The delayed groups received intravenous zoledronic acid when either post-baseline lumbar spine or total hip T score decreased to less than -2.0 or a non-traumatic clinical fracture occurred