The enhanced secretion of PTHrP regulated by ERα from BMET-derived tumor cells, in particular, suggests: (1) ERα expression in ER+ cells metastatic to bone - rather than being just a biomarker for BMETs - may also be a potential molecular driver of osteolysis and metastatic progression in bone; and/or (2) either a subpopulation of highly PTHrP-expressing cells preferentially formed BMETs and/or the bone microenvironment altered the phenotype of bone-disseminated tumor cells to favor PTHrP-mediated osteolysis. Here, ESR1 is linked to neoplasm.