Background The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a non-amplified MAF gene in the primary tumor and benefit from adjuvant zoledronic acid (ZA). Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study. Methods A retrospective analysis of MAF gene status in NSABP B-34 was performed. Eligible patients were randomly assigned to standard adjuvant systemic treatment plus 3-years oral clodronate (1600mg/daily) or placebo. Tumors were tested for MAF gene amplification, and analyzed for their relationship to clodronate for disease-free survival (DFS) and overall survival (OS) in MAF non-amplified patients. All statistical tests were 2-sided. Results . MAF status was assessed in 2,533 available primary tumor samples from 3,311 patients. Of these, 37 withdrew consent; in 77 samples no tumor was found; 536 assays did not meet quality standards, leaving 1,883 (77.8%) evaluable for MAF assay by fluorescence in situ hybridization (947 from placebo, and 936 from clodronate arms). At 5 years, in MAF non-amplified patients receiving clodronate, DFS improved by 30% (hazard ratio =0.70, 95% confidence interval = 0.51-0.94, P=0.02). OS improved at 5 years (hazard ratio =0.59, 95% confidence interval = 0.37–0.93, P=0.02) remaining statistically significant for clodronate throughout study follow-up. Conversely, adjuvant clodronate in women with MAF-amplified tumors was not associated with benefit, but possible harm in some subgroups. Association between MAF status and menopausal status was not seen. Conclusions Non-amplified MAF showed statistically significant benefits (DFS and OS) with oral clodronate, supporting validation of the AZURE study.