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The receptor activator of nuclear factor-κB (RANK) and its ligand RANKL are members of the tumor necrosis factor (TNF) super-family of cytokines with a role in progestogen-associated malignancies in breast. Basic and clinical data support the participation of the cytokine pathway in metastatic disease and as poor prognosis markers. The value of RANK/RANKL as prognostic indicators in endometrial and ovarian tumors, as well as the data suggesting a potential role of RANK/RANKL in hormone dependent tumorigenesis in the endometrium, have been described. The D-CARE study could not confirm benefit in the modulation of RANKL in breast cancer.

The RANKL/RANK system in female reproductive organ tumors: A preclinical and clinical overview