The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a nonamplified gene in the primary tumor and benefit from adjuvant ZA. Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study.

A retrospective analysis of gene status in NSABP B-34 was performed. Eligible patients were randomly assigned to standard adjuvant systemic treatment plus 3 years oral clodronate (1600 mg/daily) or placebo. Tumors were tested for gene amplification and analyzed for their relationship to clodronate for disease-free survival (DFS) and overall survival (OS) in nonamplified patients. All statistical tests were 2-sided .

status was assessed in 2533 available primary tumor samples from 3311 patients. Of these, 37 withdrew consent; in 77 samples, no tumor was found; 536 assays did not meet quality standards, leaving 1883 (77.8%) evaluable for assay by fluorescence in situ hybridization (947 from placebo and 936 from clodronate arms). At 5 years, in nonamplified patients receiving clodronate, DFS improved by 30% (hazard ratio = 0.70, 95% confidence interval = 0.51 to 0.94; =.02). OS improved at 5 years (hazard ratio = 0.59, 95% confidence interval = 0.37 to 0.93; =.02) remaining statistically significant for clodronate throughout study follow-up. Conversely, adjuvant clodronate in women with -amplified tumors was not associated with benefit but rather possible harm in some subgroups. Association between MAF status and menopausal status was not seen.

Nonamplified showed statistically significant benefits (DFS and OS) with oral clodronate, supporting validation of the AZURE study.