• 7-trial meta-analysis looking at a total of 8,735 patients treated with adjuvant bisphosphonates.
• Significant DFS risk reduction was observed (18%) with greater benefit seen in 5 ZOL trials (24%).

This meta-analysis of 7 trials appears to confirm what was gleaned from the AZURE study, namely that postmenopausal women benefit from adjuvant bisphosphonates. In spite of this finding, the current message from the investigator community clearly is that bisphosphonates should be used only in patients with bone loss. This raises the question, why are we ignoring the data given that a reduction in risk of recurrence of this magnitude for a patient with, for example, multiple involved nodes might yield an absolute additional reduction in risk of as much as 6%? Studies have shown that many patients would receive cytotoxic chemotherapy for this type of relatively minimal tradeoff. My hunch is that oncologists are downplaying these data because many are suspicious of what some of us call “the Peto effect.” For those of you who missed the 1985 NIH Consensus Development Conference on Early Breast Cancer, Richard (later to become Sir Richard) Peto, in presenting the very first international breast cancer meta-analysis of adjuvant treatment, educated the cancer research community about the importance of having enough events to determine whether an advantage exists with therapies with “modest but humanly important benefits.” This ushered in an era of enormous (and resource-draining) clinical trials — some from industry and others from the public sector — and we have now become used to data sets with statistically significant survival benefits of a few weeks leading to drug approvals. This has perhaps produced a new generation of skeptics (like me) who simply flat out don’t believe everything they read. However, Sir Richard has not left the bone scene. Looming in the background of this long-standing issue is a huge maturing adjuvant trial of denosumab in patients with node-positive and other high-risk tumors, and it could be that this and other data will someday push all of us to reconsider this treatment strategy.