• Randomized study of 5 years of adjuvant zoledronic acid (n = 3,360).
• No advantage in overall population but significant benefit in invasive DFS (p = 0.02) and overall survival (p = 0.04) for postmenopausal women; apparent harm in pre- and perimenopausal women.

At the December 2010 San Antonio Breast Cancer Symposium the bisphosphonate train (which had been gaining significant momentum since Dr Michael Gnant’s ASCO 2008 plenary presentation of the ABCSG-12 trial) started careening off the tracks when the much-awaited AZURE study failed to demonstrate the antitumor benefit of adjuvant zoledronic acid. This was followed last year by the negative results of what had been hoped to be the saving grace of the field, NSABP-B-34, which evaluated the not-too-potent oral agent clodronate. Today, most people consider the issue to be dead. However, some diehards believe the devil may be in the details and that women in estrogen-deprived states like the Austrian patients who received LHRH agonists or the postmenopausal women in AZURE (discussed in this paper) may derive benefit from adjuvant bisphosphonates. For practice right now the matter seems to be straightforward: Bisphosphonates should be used in the adjuvant setting only for women with significant bone loss.