Lack of evidence for fracture prevention in early breast cancer bisphosphonate trials: A meta-analysis.

Gynecologic oncology 2010 Jan 8; In press

Valachis A, Polyzos N NP, Georgοulias V, Mavroudis D, Mauri D

PACMeR: Medical Oncology and Obstetrics and Gynaecology, Lamia, Greece; Department of Medical Oncology, University General Hospital of Heraklion, Greece.

OBJECTIVES: Recent data suggest that fractures might affect quality of life and survival in early breast cancer patients. Bisphosphonates are effective in treatment and prevention of cancer treatment-induced bone loss, but their value in the prevention of fractures is still investigational. Our aim was to evaluate the fracture rate in breast cancer patients receiving adjuvant bisphosphonates compared with those receiving no treatment or placebo. METHODS: Our study is a systematic review and meta-analysis of randomized clinical trials. Trials were located through PubMed, ISI, Cochrane Library and major cancer scientific meetings searches. We identified 21 potentially eligible trials. Of these, 14 studies reported fracture data and were included in the analyses. Overall, 7461 early breast cancer patients were randomized, 3691 received bisphosphonates and 3770 received either placebo or no treatment. RESULTS: Adjuvant breast cancer treatment with bisphosphonates did not reduce the fracture rate compared to placebo or no use either in intent to treat analysis (12 trials, OR=0.99, 95% CI=0.73-1.34, p=0.932) and in comprehensive analysis (all 14 trials included, OR=0.84, 95% CI=0.65-1.09 p=0.197). Treatment with bisphosphonates was not beneficial in postmenopausal patients (7 trials, OR=0.82, 95% CI=0.55-1.20 p=0.298) and in patients receiving aromatase inhibitors (6 trials, OR=0.79, 95% CI=0.53-1.17 p=0.242). CONCLUSION: Our meta-analysis provides substantial evidence that bisphosphonates in the adjuvant setting among women with breast cancer do not decrease the number of fractures compared with placebo or no treatment.

Keywords: bisphosphonate breast cancer