Bone-Targeted Agents and Skeletal-Related Events in Breast Cancer Patients with Bone Metastases: The State of the Art

Abstract

Most women with advanced breast cancer will develop bone metastases, which are associated with the development of skeletal-related events (sres) such as pathologic fractures and spinal cord compression. This article reviews the evolving definition and incidence of sres, the pathophysiology of bone metastases, and the key evidence for the safety and efficacy of the currently available systemic treatment options for preventing and delaying sres in the setting of breast cancer with bone metastases. The bisphosphonates are structural analogues of endogenous pyrophosphate; three of them (clodronate, pamidronate, and zoledronate) are currently approved for use in Canada in the setting of breast cancer with bone metastases. Denosumab is a fully human immunoglobulin G2 monoclonal antibody that binds to human rankl (receptor activator of nuclear factor κB ligand), thereby preventing osteoclast formation, function, and survival, and reducing cancer-induced destruction of bone. Denosumab has recently been approved in Canada for reducing the risk of sres from the bone metastases associated with a variety of malignancies, including breast cancer. How to predict the patients that will benefit most from prophylactic treatment, the agents to select and the timing of switches between agents, the dosing schedules and durations of treatment to choose, the potential utility of the agents in the adjuvant setting, and the utility of additional endpoints such as markers of bone resorption are among the outstanding questions with respect to the optimal use of antiresorptive agents for patients with breast cancer and bone metastases.

PTHrP-Induced Refractory Malignant Hypercalcemia in a Patient With Chronic Lymphocytic Leukemia Responding to Denosumab

“…10 These studies, coupled with the patient's clinical course, suggests that hypercalcemia in CLL and other hematologic malignancies associated with PTHrP expression may benefit from denosumab therapy, especially in the setting of bony lesions and RANKL expression. 11 Our patient developed mycobacterial pneumonia and chose to undergo hospice care. We were unable to establish long-term disease control in this patient.…”

Long-term benefits versus side-effects from bone-targeted therapies for cancer patients

“…Rates of ONJ are similar with bisphosphonates and denosumab in clinical trials [51]. However, in some series, the real-world rates of ONJ are far higher than the 0-4% reported in controlled trials [46,47]. Although cumulative dose and duration of therapy are the most important risk factors for ONJ, tooth extractions, dental implant placement, periodontal procedures and infections, all contribute to osseous injury [38,49,50].…”

“…Osteonecrosis of the jaw (ONJ) is related not only to bone-targeted therapy, but also to dental trauma [38,[46][47][48][49][50]. Rates of ONJ are similar with bisphosphonates and denosumab in clinical trials [51].…”

Cost Implications of Unwarranted Imaging for Distant Metastasis in Women with Early-Stage Breast Cancer in Ontario

“…The greater frequency of bone scans could be related to the fact that bone is the most common site of breast cancer recurrence 12 ; however, fewer than 2% of asymptomatic patients with pathology-confirmed stage ii disease will have radiologic evidence of overt bone metastases 5 .…”