Abstract

Bone is the most common site for distant spread of breast cancer. Following a diagnosis of metastatic bone disease, patients can suffer from significant morbidity because of pain and skeletal related events (SRES). Bisphosphonates are potent inhibitors of osteoclastic function and the mainstay of bone-directed therapy for bone metastases. The aims of bisphosphonates are to prevent and delay SRES, to reduce bone pain, and to improve quality of life. Bisphosphonate therapy appears to have revolutionized treatment of bone metastases, but bisphosphonate use has several limitations. Those limitations include the high cost of the agents and the need for return trips to the clinic for intravenous treatment. Moreover, many uncertainties surround bisphosphonate use-for example, the timing of bisphosphonate initiation, the choice of bisphosphonate to use, the optimal duration of treatment, and the appropriate means to identify patients who will and will not benefit. In addition, potentially serious adverse effects have been associated with bisphosphonate use-for example, renal toxicity, gastrointestinal side effects, and osteonecrosis of the jaw. The present review is intended as a primer for oncology specialists who treat patients with bone metastases secondary to breast cancer. It focuses on bisphosphonate treatment guidelines, the evidence for those guidelines, and a discussion of new therapeutic agents. It also discusses the use of biochemical markers of bone metabolism, which show promise for predicting the risk of a patient's developing a SRE and of benefiting from bisphosphonate treatment.

Highlights

  • Bone is the most common site of breast cancer recurrence [1,2]

  • Starting BPs in women with only an abnormal bone scan but without evidence of bone destruction is not recommended

  • Another trial demonstrated the superiority of zoledronic acid (4 mg intravenously over 15 minutes) over pamidronate (90 mg intravenously over 2 hours); patients treated with zoledronic acid had an increased time to first skeletal related events (SREs) (p = 0.013) and fewer SREs (p = 0.58) 29

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Summary

INTRODUCTION

Bone is the most common site of breast cancer recurrence [1,2]. Up to two thirds of patients with bone metastasis will subsequently develop an skeletal-related event (SRE), defined as any of pathologic fracture, a requirement for surgical intervention and palliative radiotherapy to bone lesions, hypercalcemia of malignancy, and spinal cord compression. Are SREs associated with significant morbidity, they negatively affect survival. SREs are associated with loss of mobility and social functioning, and reduction in quality of life (QOL) 2. Treatment of bone metastases ideally involves a multidisciplinary team, including medical oncologists, radiation oncologists, palliative care specialists, and orthopedic surgeons. Systemic treatment aimed at delaying the progression of bone metastases may include endocrine therapy, biologic agents, chemotherapy, and oral or intravenous bisphosphonate therapy. New osteoclast inhibitors are currently under investigation and may offer alternative treatment options for these patients in the future

BISPHOSPHONATES
Bisphosphonate Trials and Meta-analyses
Results
Conclusions
Uncertainties About Bisphosphonate Use in Clinical Practice
Which Patients Benefit Most from Bisphosphonate Use?
CHOOSING A BISPHOSPHONATE
OPTIMAL DURATION OF BISPHOSPHONATE TREATMENT
MARKERS OF BONE RESORPTION
NEW AGENTS TARGETING THE MECHANISM OF BONE METASTASES
SUMMARY

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