TNFSF11 and breast cancer: Bone is the subject of constant turnover with bone homeostasis being regulated by the activity of bone-resorbing osteoclasts and bone-forming osteoblasts.3 Disseminated and reactivated breast cancer cells secrete parathyroid hormone–related protein (PTHrP), which triggers osteoblasts to increase their synthesis and secretion of receptor activator of NF-κB ligand (RANKL), as well as reduce their secretion of osteoprotegerin (OPG) (an orphan receptor for RANKL).