The estrogen metabolite 2-methoxyestradiol (2ME2) has emerged as a promising anticancer agent due to its potent growth-inhibitory and proapoptotic effects on tumor cells. In this issue, Cicek and colleagues demonstrate that 2ME2 inhibits tumor growth in bone marrow and soft tissues, tumor cell metastasis to bone, and tumor-induced osteolysis in vivo in a mouse model of estrogen receptor�negative metastatic breast cancer. Furthermore, the authors document that 2ME2 induces apoptosis of mononuclear TRAP-positive cells and multinucleated osteoclasts, revealing a mechanism by which 2ME2 reduces tumor-induced osteolysis. These findings concluded that the ability of 2ME2 to target tumor growth, metastasis to bone, and osteolysis are of considerable clinical significance. These exciting data support a novel therapeutic approach to treatment of advanced breast cancer. For details, see the article by Cicek and colleagues on page 10106 of this issue.