Taken together, these findings suggest that TGFβ-stimulated Smad signaling, which is active in 75% of clinical BMET [29,60], may be a biomarker and/or necessary driver of osteolysis in ER+ BMETs, the absence of which may account, at least in part, for a lack of progression of osteolysis and tumor expansion in mice inoculated with T47D or ZR-75-1 cells, despite evidence here, and in prior studies, that these tumor cells disseminate to bone [61,62]. This evidence concerns the gene TGFB1 and neoplasm.