A, Mice prepped with estrogen (E2) pellets were injected with 5×106 BT474/AZ-LR cells and treated with L until randomization to 5 groups: E2+L, E2+Afa, ED+Veh, ED+L, and ED+Afa (for details see Materials and Methods). B, Kaplan-Meier analyses of progression-free survival within 16 days of treatment of E2+Afa or E2+L. Tumor progression was defined as tumor size tripling since randomization. TTP: time to tumor progression. C, Kaplan-Meier analyses of progression-free survival and tumor regression (graph showing change of proportion of non-regressing tumors) within 85 days of ED+Veh, ED+L, or ED+Afa treatment. Tumor regression was defined as tumor size halving since the day of randomization. TTR: time to tumor regression. D, p-HER2 (Y1221), p-AKT (S473), and p-p44/42 MAPK (T202/Y204) levels of xenografts in each treatment arm was assessed by IHC and scored as H-score by a pathologist. Two tumors (Suppl. Fig. S8B and S8C) that were resistant to the ED+Afa regimen were not included in the analysis. *: p<0.05, **: p<0.01, ***: p<0.001.