ESR1 and breast cancer: Thus, additional bone-specific molecular targets downstream of ERα, in addition to those that drive proliferation, may complement existing therapeutics for the treatment of osteolytic ER+ BMETs, particularly for HT-resistant metastatic ER+ breast cancer, while potentially providing a mechanistic basis for the long-standing clinical observation of the association of tumoral ERα expression with breast cancer metastatic risk specific to bone.