Total systemic blockade of TGF-β signaling pathway by neutralizing antibodies against TGF-β or small molecule inhibitors against the type I TGF-β receptor kinase activity prevents bone metastases in preclinical models [12], [13] but may cause off-target effects because TGF-β has many functions in normal physiology as well as tumor suppressing effects during early stages of breast cancer. This evidence concerns the gene TGFB1 and breast cancer.