a) Normal breast epithelium (HMEC and MCF10A), localized breast cancer (BT474, HCC1954, and BT549), and lung metastatic breast cancer (MCF7, T47D, SKBR3, and MDA-MB-231) cells are used to model different stages of breast cancer progression. To model diseased lung, normal lung epithelium (HTBE) and localized lung cancer (A549 and H460) cells are used. b) Schematic diagram representing breast cancer lung permissive changes calculation. First, for both breast and lung, cancer cell compartment identity is compared with the normal epithelial cell. This results in four possible compartment identity combinations: AA (A compartment in both normal and cancer), AB (A compartment in normal and B compartment in cancer), etc. Then, a cross-comparison between the breast and lung systems leads to 16 compartment identity combinations. Two specific combinations: AB_BB and BA_AA are defined as lung permissive changes (yellow arrows). c) Fraction of lung permissive changes shown by localized and metastatic cancers from different breast cancer subtypes. d-f) TCGA patient gene expression (left) and GO term enrichment (biological processes) (right) for genes from regions exhibiting (d) BA_AA lung permissive changes in the luminal metastatic breast cancer subtype, (e) AB_BB lung permissive changes in case of HER2-enriched metastatic breast cancer subtype, or (f) BA_AA lung permissive changes in case of triple-negative metastatic breast cancer subtype. TCGA data from BRCA and LUAD tumor vs. normal sets used and sample size indicated.