Repurposing denosumab in breast cancer beyond prevention of skeletal related events: Could nonclinical data be translated into clinical practice?

Denosumab is a human monoclonal antibody inhibiting the receptor activator of nuclear factor kappa-B ligand (RANKL). Initially approved as antiosteοporotic agent, denosumab is being currently pursued as a candidate for drug repurposing in oncology, especially breast cancer. The present review provides an overview of the therapeutic potential of denosumab in breast cancer beyond prevention of skeletal-related events (SREs), with focus on prevention of carcinogenesis in BRCA mutation carriers and on adjuvant treatment in early breast cancer patients. Study search was conducted on the following electronic databases: PubMed, Google scholar, Scopus.com, ClinicalTrials.gov, and European Union Clinical Trials Register from 2008 until June 2020. Nonclinical data have established links between RANKL signaling and breast cancer initiation and progression, rationalizing exploring the potential bone-independent anticancer role of denosumab beyond SREs prevention. Preclinical and preliminary clinical data show that denosumab may inhibit carcinogenesis in BRCA mutation carriers. Denosumab adjuvant in early breast cancer has been shown, though inconsistently, to provide a disease-free survival benefit for a subgroup of patients. Despite promising results, the incorporation of denosumab in preventive and therapeutic protocols of breast cancer beyond prevention of SREs cannot be endorsed until further research consolidates its efficacy. [ABSTRACT FROM AUTHOR]