The big news in December 2015 for breast cancer is that adding a bone strengthening agent to post-operative therapy reduces cancer-specific mortality by a shocking 18%. First the background: for years there has been a suspicion that agents that prevent osteoporosis — classically Fosamax and its various bisphosphonate first cousins — could also prevent bone metastasis. There were data published almost twenty years ago that supported this theory but confirmatory evidence was hard to come by. At the 2015 San Antonio Breast Cancer Symposium Gnant and colleagues from Vienna presented their results from a large trial in which half of newly diagnosed breast cancer patients received Denosumab, a relatively new bone strengthening agent with a different mechanism of action from the bisphosphonates, and the other half placebo. Over 3000 women were enrolled; all had hormone-receptor positive tumors (expected to do better than those that are hormone-receptor negative). As also reported in a parallel study by the same authors, fracture rates were 50% lower — no surprise — but the big news was an overall reduction of mortality of 18%, not explained by a reduction in fractures. In the world of oncology, where a 5% uptick in survival is big news, this is very big news. Dr. Stark comments, “The big tease is over; bone-strengthening agents do reduce mortality in newly diagnosed breast cancer patients. The reason is unknown but may relate to the creation of a microenvironment in the bone hostile to the implantation and growth of metastatic deposits. Other than cost, the addition of either Denosumab or a bisphosphonate now seems like the new standard of care. Based on the mature data in this trial, the former is probably preferred. Also, there is probably a lower risk of developing osteonecrosis of the mandible with Denosumab than with bisphosphonates, although that risk is likely not zero. Kudos to these investigators for their analysis!”