Fig. 1: M/D-driven tumors recapitulate key features of human HR⁺ breast cancer.

a Schedule of oncogenic challenges for the induction of M/D-driven tumors and representative images of M/D-driven tumors established in WT C57BL/6 mice. Scale bar = 1 cm. b Tumor-free survival (TFS) and time-to-death (TTD) in WT C57BL/6 mice subjected to M/D-driven oncogenesis. Number of mice is reported. c Representative histology of M/D-driven tumors as compared to human HR⁺ breast cancers. Scale bar = 50 µm. d Probeset distribution comparing the transcriptomic profile of 6 M/D-driven mammary tumors established in C57BL/6 mice with that of human breast cancers from the TCGA public database. Probability of molecular subtyping is reported for each mouse tumors. e, f TFS and overall survival (OS) of WT C57BL/6 mice and C57BL/6 bearing ER mutations that cause nuclear exclusion (e) or nuclear accumulation (f) subjected to M/D-driven oncogenesis. Number of mice, hazard ratio (HR) and p values (two-sided log-rank) are reported. g TFS and OS of WT C57BL/6 mice subjected to M/D-driven oncogenesis in control conditions or along with tamoxifen administration in the drinking water. Number of mice, HR and p values (two-sided log-rank) are reported. h. Non-supervised hierarchical clustering of the transcriptomic profile of M/D-driven tumors established in WT C57BL/6 mice (n = 6), mammary glands exposed to M/D but not developing tumors (n = 6) and M/D-naïve mammary glands (n = 6). Gene Ontology analysis, fold change (FC) and adjusted, two-sided p values are reported. Red, upregulation. Yellow, downregulation. i Relative amount of CD3⁺, CD8⁺, CD4⁺ and CD25⁺FOXP3⁺ cells infiltrating M/D-driven tumors in C57BL/6 mice vs syngeneic M/D-naïve mammary glands. Results are means ± SEM plus individual data points. Number of mice and p values (unpaired, two-sided Student’s t, as compared to M/D-naïve mammary glands) are reported.