Sometimes advances in treatment come suddenly with the results of one major trial, but in the case of bisphosphonates--drugs used to treat bone thinning or bone metastases--the information has been trickling in slowly. For over a decade, studies in early-stage breast cancer have hinted that the risk of metastatic recurrence can be lowered with bisphosphonates. We still don't know exactly how a bone-targeting drug could prevent recurrence. One clue comes from that fact that these drugs seem to lower the number of microscopic cancer cells that are sometimes seen in the bone marrow of patients--even those that may never actually develop metastases. However, patients who harbor these so called "micrometastases" do have a higher risk of developing breast cancer. It has been postulated that the bone may serves as the "soil" to support the "seed," in this case tumor cells, that can then go on to form metastases. It is therefore thought that bisphosphonates, which are known to lower the resorption and turnover of bone minerals, may therefore make the "soil" less hospitable to tumor cells.However, large randomized clinical trials of bisphosphonate therapy using the more potent newer generation amino-bisphosphonates such as Zometa (zoledronic acid) have yielded mixed results--some showing fewer recurrences and others showing no effect at all.Finally, a clearer picture appears to be emerging from analyzing all these trials together, as was recently done in what is called an overview (or meta-) analysis. A pooling of the results of trials that involved nearly 23,000 patients demonstrates that the main impact is in post-menopausal women, or those that have their ovaries suppressed with medical therapy. In these patients, the death rate is lowered by about 3 percent over 10 years. While this difference may seem modest, it is in the same range of what some chemotherapy treatments provide for early-stage breast cancer. It is unlikely that more trials of this nature will be done, although we still await results and updates from some of these studies. The big question will be whether the medical community (and insurance companies) will heed the results of this meta-analysis when many of the individual trials were negative. This remains to be seen as revised guidelines in this area are currently being formulated by the American Society of Clinical Oncology.