American Society of Clinical Oncology guideline on the role of bisphosphonates in breast cancer

Purpose: To determine clinical practice guidelines for the use of bisphosph onates in the prevention and treatment of bone metastases in breast cancer and their role relative to other therapies for this condition. Methods: An expert multidisciplinary panel reviewed pertinent information h am the published literature and meeting abstracts through May 1999. Additio nal data collected as part of randomized trials and submitted to the United States Food and Drug Administration were also reviewed,and investigators w ere contacted for more recent information. Values for levels of evidence an d grade of recommendation were assigned by expert reviewers and approved by the panel. Expert consensus wets used if there were insufficient published data. The panel addressed which patients to treat and when in their course of disease, specific drug delivery issues, duration of therapy, management of bony metastases with other therapies, and the public policy implication s. The guideline underwent external review by selected physicians, members of the American Society of Clinical Oncology (ASCO) Health Services Researc h Committee, and the ASCO Board of Directors. Results: Bisphosphonates have not had an impact on the most reliable cancer end point: overall survival. The benefits have been reductions in skeletal complications, ie, pathologic fractures, surgery for fracture or impending fracture, radiation, spinal cord compression, and hypercakemia. Intravenou s (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in patients with metastatic breast cancer who have imaging evid ence of lytic destruction of bone and who are concurrently receiving system ic therapy with hormonal therapy or chemotherapy For women with only an abn ormal bone scan but without bony destruction by imaging studies or localize d pain, there is insufficient evidence to suggest starting bisphosphonates. Starting bisphosphonates in patients without evidence of bony metastasis, even in the presence of other extraskeletal metastases, is not recommended. Studies of bisphosphonates in the adjuvant setting have yielded inconsiste nt results. Starting bisphosphonates in patients at any stage of their nono sseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended. Oral bisphosphonates are one of several options which can be used for preservation of bone density in p remenopausal patients with treatment induced menopause. The panel suggests that,once initiated, N bisphosphonates be continued until evidence of subst antial decline in a patient's general performance status. The panel stresso r that clinical judgment must guide what is a substantial decline. There is no evidence addressing the consequences of stopping bisphosphonates after one or more adverse skeletal events. Symptoms in the spine, pelvis, or femu r require careful evaluation for spinal cord compression and pathologic fra cture before bisphosphonate use and if symptoms recur, persist, or worsen d uring therapy. The panel recommends that current standards of care for canc er pain, analgesics and local radiation therapy, not be displaced by bispho sphonates. N pamidronate is recommended in women with pain caused by osteol ytic metastasis to relieve pain when used concurrently with systemic chemot herapy and/or hormonal therapy, since it wets associated with a modest pam control benefit in controlled trials. Conclusion: Bisphosphonates provide a meaningful supportive but not life-pr olonging benefit to many patients with bone metastases from cancer. Further research is warranted to identify clinical predictors of when to start and stop therapy, to integrate their use with other treatments for bone metast ases, to identify their role in the adjuvant setting in preventing bone met astases, and to better determine their cost-benefit consequences. (C) 2000 by American Society of Clinical Oncology.