In breast cancer, tumor-derived factors, including parathyroid hormone-releasing protein (PTHrP), prostaglandin E2 (PGE2), TNFα, and interleukins (e.g, IL-1, IL-6, IL-11), have been demonstrated to enhance RANKL expression by osteoblasts and other bone stromal cells present, which may directly contribute to osteoclastogenesis29,30. This evidence concerns the gene IL6 and neoplasm.