The improvement in overall survival that was observed in our study has not been seen in other trials of first-line hormonal therapy for HR-positive metastatic breast cancer.23-27 Specifically, in the trials comparing aromatase-inhibitor therapy with tamoxifen therapy, the benefit from aromatase inhibitors with respect to progressionfree survival failed to translate into a benefit with respect to overall survival, a finding that was attributed to the crossover of some patients in the tamoxifen group to an aromatase inhibitor. In contrast, the results of our study are not confounded by crossover to combination therapy, and the benefit with respect to overall survival closely mirrored the benefit with respect to progressionfree survival (hazard ratio, 0.81 and 0.80, respectively). A study comparing low-dose fulvestrant with tamoxifen did not show a between-group difference in progression-free survival or overall survival, suggesting that the combination therapy, rather than fulvestrant therapy alone, mediated the improvement in our study.3