Beyond the anticipated primary prevention impact that denosumab-targeted aberrancies in the RANKL pathway might play in BRCA1 mutation carriers [64], preliminary evidence from the ABCSG 18 trial showing improved disease-free survival of women receiving adjuvant denosumab [65, 66] and currently ongoing clinical investigations of denosumab as an adjunct to neoadjuvant chemotherapy [67] should begin to clarify the role of RANKL blockade to prevent CSC-driven tumor recurrence and metastasis in non-BRCA1 patients. The gene discussed is BRCA1; the disease is neoplasm.