Coleman R, Finkelstein DM, Barrios C, et al. - Given that preclinical evidence demonstrates a possible influence of denosumab [a fully human monoclonal antibody that binds to, and inhibits, the receptor activator of RANKL (TNFSF11)] on breast cancer biology, researchers determined if denosumab combined with standard-of-care adjuvant or neoadjuvant systemic therapy and locoregional treatments would lead to an increase in bone metastasis-free survival in women with breast cancer. Including patients from 389 centres in 39 countries, they conducted this international, double-blind, randomised, placebo-controlled, phase 3 study (D-CARE). Eligible patients were centrally randomly allocated (1:1) to receive either denosumab (120 mg) or matching placebo subcutaneously every 3–4 weeks, initiating with neoadjuvant or adjuvant chemotherapy, for approximately 6 months and then every 12 weeks for a total time frame of 5 years. Findings revealed no improvement in disease-related outcomes was provided by denosumab for women with high-risk early breast cancer, despite preclinical evidence proposing a likely delay in bone metastasis or disease recurrence as a result of RANKL inhibition in patients with early-stage breast cancer.