Optimal management of bone metastases in breast cancer patients

Abstract

Bone metastasis in breast cancer is a significant clinical problem. It not only indicates incurable disease with a guarded prognosis, but is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression, and hypercalcemia. In recent years, the mechanism of bone metastasis has been further elucidated. Bone metastasis involves a vicious cycle of close interaction between the tumor and the bone microenvironment. In patients with bone metastases, the goal of management is to prevent further skeletal-related events, manage complications, reduce bone pain, and improve quality of life. Bisphosphonates are a proven therapy for the above indications. Recently, a drug of a different class, the RANK ligand antibody, denosumab, has been shown to reduce skeletal-related events more than the bisphosphonate, zoledronic acid. Other strategies of clinical value may include surgery, radiotherapy, radiopharmaceuticals, and, of course, effective systemic therapy. In early breast cancer, bisphosphonates may have an antitumor effect and prevent both bone and non-bone metastases. Whilst two important Phase III trials with conflicting results have led to controversy in this topic, final results from these and other key Phase III trials must still be awaited before a firm conclusion can be drawn about the use of bisphosphonates in this setting. Advances in bone markers, predictive biomarkers, multi-imaging modalities, and the introduction of novel agents have ushered in a new era of proactive management for bone metastases in breast cancer.

DLC1-dependent parathyroid hormone–like hormone inhibition suppresses breast cancer bone metastasis

“…In addition, we observed an organ-specific correlation of DLC1 expression with bone metastasis. Interestingly, we also found in the NKI dataset that DLC1 silencing was associated with bone metastasis only for luminal-type breast tumors (Supplemental Figure 9G), which are known to be predisposed to bone recurrence (42,43), although such findings need to be validated in additional datasets. Previous studies have shown the association of DLC1 silencing with poor prognosis in breast cancer (15).…”

Potential of targeted drug delivery system for the treatment of bone metastasis

“…In osteolytic lesions, the bone resorption rate exceeds that of bone formation, whereas in osteoblastic lesions, the bone formation rate is faster (Wong & Pavlakis, 2011).…”

“…Recently, in comparison to zoledronic acid, denosumab was found to be more effective in delaying skeletal-related events in both metastatic breast cancer and prostate cancer. Furthermore, its fewer acute-phase reactions, such as fever, myalgia or arthralgia, and lesser renal toxicity makes it favorable candidate for the treatment of bone metastases and opens wide opportunities for developing efficient drug delivery systems in this direction (Wong & Pavlakis, 2011).…”

“…Both the National Comprehensive Cancer Network and American Society of Clinical Oncology do not endorse routine blood tests, tumor markers or imaging studies for surveillance (Wong & Pavlakis, 2011). Wong & Pavlakis (2011) has also stated that the current model on bone metastasis detection, prevention and treatment is ''reactive'' rather than proactive.…”

“…Furthermore, the consequences have been found to be so drastic that only 20% of patients with breast cancer are still alive five years after the discovery of bone metastasis (Roodman, 2004). Wong & Pavlakis (2011) have reported it as an incurable disease, which is also associated with skeletal-related morbidities including bone pain, pathological fractures, spinal cord compression and hypercalcemia.…”