Fig. 1

Z-endoxifen and standard endocrine therapies efficacy on AI-sensitive and AI-resistant tumors growth in vivo. a Four- to 6-week-old female ovariectomized BALB/c athymic female nude mice were subcutaneously injected with 2.5 × 10⁶ MCF7AC1 cells in 100 μl of 1:1 phosphate-buffered saline (PBS) to Matrigel mixture in the right and left flanks. When tumor volumes reached ≥ 300 mm³, mice were randomized (n = 30 mice/group) to control, letrozole (10 μg/day), tamoxifen (500 μg/day), or Z-endoxifen (25 mg/kg and 75 mg/kg) treatment. Tumor volume was assessed every week for a period of 4 weeks. Data are presented as mean ± SEM. b The area under the tumor volume growth curve (AUC), adjusted for baseline, was calculated through 4 weeks of treatment; AUC distributions by treatment group are shown with side-by-side boxplots and were compared between groups using Wilcoxon rank-sum tests. c Six- to seven-week-old female nude mice were injected with 2.2 × 10⁶ MCF7LR cells in the right flank. When tumor volumes reached ≥ 150 mm³, mice were randomized (n = 12 mice/group) to letrozole, Z-endoxifen (50 mg/kg), exemestane (250 μg/day) alone, or exemestane plus everolimus (2.5 mg/day). Tumor volume was measured every week. Data are presented as mean ± SEM. d The area under the tumor volume growth curve (AUC), adjusted for baseline, was calculated through 63 days (9 weeks) of treatment; AUC distributions by treatment group are shown with side-by-side boxplots and were compared between groups using Wilcoxon rank-sum tests. Non-significant (ns), P > 0.05; *P < 0.05; **P < 0.01; ***P < 0.001