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Is clodronate an effective adjuvant treatment in breast cancer?



DOI:10.1038/bonekey.2012.159

Bisphosphonates such as clodronate may change the bone microenvironment by acting on osteoclasts, so inhibiting the formation of bone metastases in the longer term. In this study, Paterson et al. conducted a randomized controlled trial in 3323 female breast cancer patients, in which 50% were given daily oral clodronate (1600 mg for 3 years) while the other 50% received a placebo.

Overall, there were no differences between the groups for disease-free survival, overall survival, recurrence-free survival or bone metastasis-free survival. However, when data from the sub-group of women over 50 were analysed, clodronate treatment increased recurrence-free survival (hazard ratio 0.75, 95% CI=0.57–0.99; P=0.045), the non-bone metastasis-free interval (0.63, 0.43–0.91; P=0.014) and the bone metastasis-free interval (0.62, 0.40–0.95; P=0.027), but there was no significant difference in overall survival (0.80, 0.61–1.04, P=0.094).

The authors suggest there may be a positive effect for clodronate in post-menopausal older women treated for breast cancer, but recommend further studies, including meta-analyses, before guidelines are prepared.

Editor's comment: Results obtained in this clinical trial accord with those of previous adjuvant trials in breast cancer, which show a relapse-free survival (and even an overall survival) benefit in post-menopausal patients receiving a bisphosphonate therapy with zoledronic acid. Further studies are needed to determine how bisphosphonates could exert anticancer effects in a low-oestrogen environment.


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