PTHLH and breast carcinoma: In a mouse model of estradiol (E2)-dependent bone metastasis of ER+ breast cancer, ERα-induced tumor secretion of the osteolytic factor PTHrP, the number of osteoclasts at the bone–tumor interface, and osteolytic bone destruction were increased in an E2-dependent manner, which may explain the tendency of ER+ tumors to form osteolytic lesions [76].