The generation of osteolytic factors (such PTHrP) and osteolysis are influenced by both genomic and nongenomic estrogen receptor signaling in tumor and bone cells; in Estrogen Receptor-positive (ER+) breast cancer models, nongenomic ER signaling might be necessary for complete osteolytic reactivation [140,141]. This evidence concerns the gene ESR1 and breast carcinoma.