Additionally, bone-derived placental growth factor (PGF) is upregulated in the presence of breast cancer cells, resulting in a decreased production of the RANK-L binding glycoprotein osteoprotegerin (OPG) from osteoblasts and stromal cells, thus stimulating the formation of osteolytic lesions due to increased RANK-L levels, which can be prevented by PGF blockade [122] (Figure 1). This evidence concerns the gene TNFRSF11B and breast cancer.