Introduction
death, skeletal adverse, breast cancer, cancer treatment-induced bone loss, DTC-positive, osteoporosis
BREAST CANCER, PROLIFERATION, RECURRENT DISEASE, BONE METASTASIS, OSTEOPOROSIS
Despite recent advances in early detection and systemic treatment, about 20–30% of patients with early breast cancer experience distant metastatic relapse. Recurrent disease can occur even years after primary treatment and constitutes the predominant cause of breast cancer specific death [Anti-resorptive agents, such as bisphosphonates, counteract osteoclast mediated bone-resorption and are widely used to treat patients, which suffer from bone metastasis induced skeletal adverse events or cancer treatment-induced bone loss and osteoporosis [The human monoclonal IgG2 antibody denosumab represents a further class of anti-resorptive agents and targets receptor activator of nuclear factor-kappaB ligand (RANKL), [Although there is a great body of pre-clinical evidence that RANK signaling promotes proliferation and (bone) metastatic progression of breast cancer [Serum RANKL levels were shown to be higher in DTC-positive compared to DTC-negative breast cancer patients and were reported to predict clinically manifest bone metastasis [