Bisphosphonates for breast cancer.

Pavlakis N, Schmidt RL, Stockler MR

Published Online:

July 16, 2008

When breast cancer has spread to the bones (bone metastases ), bisphosphonate drugs (added to anti-cancer treatment for breast cancer) can reduce pain, fractures and other bone problems. Women and men with advanced breast cancer commonly develop bone metastases. Cancer in bones can cause pain, fractures, hypercalcaemia (too much calcium in the blood) and spinal cord compression. This is because cancer deposits can erode into bone using bone-absorbing cells. Bisphosphonates are drugs that reduce the activity of these bone-absorbing cells. This review of trials in women with advanced breast cancer with bone metastases found that the use of bisphosphonates (in addition to their other cancer treatments) can reduce these serious bone problems. Adverse effects are not common, and include mild gut reactions, transient fever and hypocalcaemia, depending on which drug is used.

Abstract (click to read)

Background:

Bone is the most common site of metastatic disease associated with breast cancer (BC). Bisphosphonates inhibit osteoclast-mediated bone resorption.

Objectives:

To assess the effect of Bisphosphonates on skeletal events (SEs), bone pain, quality of life (QOL) and survival in women with early (E) and advanced breast cancer (ABC).

Search strategy:

The specialised register maintained by the Cochrane Breast Cancer Group was searched January 2007. Additional handsearching was conducted of journals and proceedings of key meetings.

Selection criteria:

Randomised studies comparing Bisphosphonates and placebo, or different Bisphosphonates in women with metastatic BC.

Data collection and analysis:

Two reviewers independently assessed trials and extracted data. Toxicity information was collected from the trials.

Main results:

Twenty one randomised studies were included. In nine studies (2189 women with ABC and existing bone metastases), compared with placebo or no bisphosphonates, bisphosphonates reduced SE risk by 17% (RR 0.83; 95% confidence interval (CI) 0.78 to 0.89; P < 0.00001). This benefit was most certain with intravenous (IV) pamidronate 90 mg (RR 0.77; 95% CI 0.69-0.87), IV zolendronate 4mg (RR 0.59; 95% CI 0.42 - 0.82) and oral (PO) clodronate 1600 mg (pooled RR 0.84; 95% CI 0.72-0.98). Direct comparison of IV zolendronate and IV pamidronate confirms at least equivalent efficacy in a single large study.

Bisphosphonates reduced SE rate in 12 studies (median reduction 28%, range 14-48%) with statistically significant reductions reported in 10 studies. Women with ABC and clinically evident bone metastases treated with Bs showed significant delays in the median time to SE. Compared with placebo or no B, treatment with Bs significantly improved bone pain in seven studies. Improvements in global QOL with Bisphosphonates compared to placebo were reported in the three ibandronate studies.

Treatment with Bisphosphonates does not appear to affect survival in women with ABC. Bisphosphonates in women with ABC without clinically evident bone metastases do not reduce SE incidence.

In three studies of PO clodronate(1653 women with EBC), skeletal metastases were not significantly reduced (RR 0.82; 95% CI 0.66-1.01; P = 0.07), and there was heterogeneity among these studies.

Reported toxicity was generally mild but osteonecrosis of the jaw has since been identified as a potential problem with long term IV Bisphosphonates highlighting a need for maintaining good oral care prior to and during treatment.

Authors' conclusions:

In women with ABC and clinically evident bone metastases, Bisphosphonates (PO,IV)) reduce the risk of developing SEs and SE rate, as well as delaying the time to SE. Some Bisphosphonates may also reduce bone pain and may improve QOL. The optimal timing and duration of treatment is uncertain.

This record should be cited as:

Pavlakis N, Schmidt RL, Stockler MR. Bisphosphonates for breast cancer. Cochrane Database of Systematic Reviews 2005, Issue 3. Art. No.: CD003474. DOI: 10.1002/14651858.CD003474.pub2

Assessed as up to date:

January 10, 2007

Find the research

Get full text at The Cochrane Library

Primary Review Group:

Breast Cancer Group

Health topics:

Cancer > Breast > Site-specific metastases

Cancer > Breast > Supportive care

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Bisphosphonates for breast cancer.

More like this

Copyright © 2012 - The Cochrane Collaboration