This trial tested the hypothesis that the combination of anastrozole and fulvestrant would delay the development of progressive disease in postmenopausal women with HR-positive breast cancer.Progression-free survival was significantly longer with the combination therapy than with anastrozole alone. The hazard ratio of 0.80 for progression or death with combination therapy was notable, especially given the fact that the group receiving anastrozole alone had a higher median progression- free survival than had been projected in the design of the trial. Both regimens were associated with mild-to-moderate toxic effects, and although grade 3 to 5 toxic effects occurred more frequently in the combination group than in the anastrozole- alone group, the between-group difference was not significant.