Bisphosphonate treatment reduces breast cancer recurrence in the bones of post-menopausal women

1. This meta-analysis showed that bisphosphonate treatment in women with breast cancer significantly reduced the risk of cancer recurrence in bone compared to placebo.

2. In post-menopausal women, bisphosphonate treatment significantly reduced the risk of breast cancer recurrence, distant cancer recurrence, cancer recurrence in bone, and breast cancer mortality, but did not significantly affect outcomes in pre-menopausal women.

Evidence Rating Level: 1 (Excellent)      

Study Rundown: Bisphosphonates are commonly used to treat osteoporosis, especially in post-menopausal women, as a way to reduce bone loss and fracture risk. Additionally, bisphosphonates can also be used to reduce the risk of fractures in metastatic cancers to bones. Previous studies using bisphosphonates for treatment of bone metastases in patients with breast cancer have shown mixed results. This meta-analysis of 18,766 women with breast cancer from 26 previous clinical trials attempted to determine whether bisphosphonates reduce the risk of bone metastases and whether menopausal status plays a role in treatment efficacy.

The results showed that bisphosphonates had a highly significant reduction in bone recurrence when compared to placebo, but had only borderline significance in the rate of cancer recurrence, distant recurrence, and breast cancer mortality. Additionally, bisphosphonate treatment in pre-menopausal women did not significantly affect outcomes, but significantly reduced recurrence, distant recurrence, bone recurrence, and breast cancer mortality in post-menopausal women. This study was strengthened by the analyses of specific subgroups within the sample population, but limited by the inability to assess the efficacy of the standard bisphosphonate treatments for osteoporosis as treatments for breast cancer.

Click to read the study in The Lancet

Relevant Reading: Adjuvant zoledronic acid in patients with early breast cancer: final efficacy analysis of the AZURE (BIG 01/04) randomised open-label phase 3 trial

In-Depth [meta-analysis]: This meta-analysis included data from 18,766 (11,767 post-menopausal) women in 26 trials. Eligible trials included those that began before 2008 and randomized women to receive either a bisphosphonate or placebo. 18,706 participants (97%) received bisphosphonates for 2-5 years. The primary endpoints were any recurrence of breast cancer, distant recurrence, and breast cancer mortality.

Bisphosphonates did not significantly reduce the rate of cancer recurrence (Rate ratio [RR] 0.94, 95% Confidence Interval [CI] 0.87-1.01; 2p=0.08), but had a borderline statistically significant reduction in the risk of distant recurrence (0.92, 0.85-0.99; 2p=0.03) and breast cancer mortality (0.91, 0.83-0.99; 2p=0.04). However, bisphosphonates had a highly significant reduction in the rate of bone recurrence compared to placebo (10-year risk 7.8% vs. 9.0%; RR 0.83, 0.73-0.94; 2p=0.004). When analyzing for menopausal status, bisphosphonates did not significantly affect any of the primary outcomes in pre-menopausal women, but significantly reduced recurrence (RR 0.86, 95% CI 0.78-0.94; 2p=0.002), distant recurrence (0.82, 0.74-0.92; 2p=0.0003), bone recurrence (0.72, 0.60-0.86; 2p=0.0002), and breast cancer mortality (0.82, 0.73-0.93; 2p=0.002) in post-menopausal women. Additionally, bisphosphonates reduced the risk of bone fractures (RR 0.85, 95% CI 0.75-0.97; 2p=0.02).

Image: PD

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