Fig. 2. BI 853520 decreases primary tumor growth in various orthotopic pre-clinical mouse models of breast cancer.

a Oral treatment of mice bearing Py2T breast tumors with daily 50 mg/kg BI 853520 dissolved in Natrosol or with Natrosol-vehicle alone from day 22 post injection (indicated by an arrow) for 25 consecutive days significantly decreased tumor volume over time. n = 10 mice per treatment cohort. b Oral treatment of mice bearing 4T1 breast tumors with daily 50 mg/kg BI 853520 dissolved in Natrosol or with Natrosol-vehicle alone from day eight post injection (indicated by an arrow) significantly decreased tumor volume over time. Tumor growth curves of individual mice are shown. Vehicle cohort, n = 7 mice; BI 853520 cohort, n = 6 mice. c Oral treatment of mice bearing MTflECad breast tumors with daily 50 mg/kg BI 853520 dissolved in Natrosol or with Natrosol-vehicle alone from day 10 post injection significantly decreased tumor volume over time (indicated by an arrow). n = 9 mice per treatment cohort. d Top: Oral treatment schedule for the treatment of MMTV-PyMT transgenic mice with vehicle, BI 853520-late (50 mg/kg daily, from 10 to 13 weeks of age) or BI 853520-early (50 mg/kg daily, from 5 to 13 weeks of age). Bottom: Normalized mammary fat pad (MFP) weights for each treatment cohort. All mice were sacrificed at 13 weeks of age, and primary tumors and lungs were used for further analysis. Vehicle cohort, n = 9; BI 853520-late, n = 9; BI 853520-early, n = 8. e Early BI 853520 treatment significantly improves tumor-free survival of MMTV-PyMT mice. Days on treatment starting from week 5 of age are shown. The time reaching termination criteria was determined for the mice treated as described in d. As shown here, at the time point of treatment initiation of the BI 853520-late group (arrow; day 35 on treatment), most mice in this group displayed palpable tumors. f Grading of primary tumors of MMTV-PyMT transgenic mice treated as described in d. Data are shown as the percentage of the average area covered by each grade of two histological sections per mouse. Early BI 853520 treatment delays malignant tumor progression (increase in hyperplasia and adenoma stage, decrease in carcinoma stage). Statistical analysis was performed by unpaired, two-tailed Mann–Whitney U test (a, c, d), by log-rank (Mantel–Cox) test (e), and unpaired, two-tailed Student’s t test (f). All data are depicted as means ± SEM. ****p < 0.0001, ***p < 0.001, **p < 0.01, *p < 0.05