Note from the National Guideline Clearinghouse (NGC): The American Society of Clinical Oncology (ASCO) has updated its 2000 recommendations on the role of bisphosphonates and bone health issues in women with breast cancer. Each recommendation from the 2000 guideline is listed below, and is followed by an updated (2003) recommendation, if applicable. "No change" is indicated if a particular recommendation has not been revised.
Bisphosphonate Use in Women With Imaging Evidence of Bone Metastases
Lytic Disease on Plain Radiographs
2000 Recommendation: Intravenous (IV) pamidronate 90 mg delivered over 1 to 2 hours every 3 to 4 weeks is recommended in women with metastatic breast cancer who have lytic destruction of bone on plain radiograph(s) and who are receiving systemic therapy with hormonal therapy or chemotherapy.
2003 Recommendation: For breast cancer patients who have evidence of bone destruction on plain radiographs, IV pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks are recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. For each of the guidelines, clinical judgment should also take into consideration the patient's general performance status and overall prognosis.
Abnormal Bone Scan, Normal Radiographs but Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) Scan Showing Bone Destruction
2000 Recommendation: Starting bisphosphonates in women with an abnormal bone scan and an abnormal CT scan or MRI showing bone destruction and localized pain, but normal plain radiographs, is considered reasonable by panel consensus based on the findings in women with osteolytic changes on plain radiographs.
2003 Recommendation: Starting bisphosphonates in women with an abnormal bone scan and an abnormal CT or MRI scan showing bone destruction, but normal plain radiographs, is considered reasonable by Panel consensus based on the findings in women with lytic or mixed lytic/blastic changes on plain radiographs.
Abnormal Bone Scan, Normal Radiographs, and No Evidence of Bone Destruction on CT or MRI
2000 Recommendation: Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bony destruction on radiographs, tomograms, CT scans, or MRI, or with localized pain, is not suggested.
2003 Recommendation: Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction on radiographs, CT scans, or MRI is not recommended.
Safety and Adverse Effects
2003 Recommendation: In patients with pre-existing renal disease and a serum creatinine level less than 3 mg/dL (265 micromoles/L), no change in dosage, infusion time, or interval of pamidronate or zoledronic acid is required. Use of these bisphosphonates among patients with worse function has been minimally assessed. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided. The Panel recommends that serum creatinine should be monitored prior to each dose of pamidronate or zoledronic acid, in accordance with Food and Drug Administration (FDA)-approved labeling. Serum calcium, electrolytes, phosphate, magnesium, and hematocrit/hemoglobin should also be monitored regularly, even though there is no evidence on which to base a recommendation for time intervals. In contrast to multiple myeloma patients, there currently is no data to support routine assessments for albuminuria in breast cancer patients.
Biochemical Markers
2000 Recommendation: The use of the biochemical markers to monitor bisphosphonate use is not suggested for routine care.
2003 Recommendation: No change
Duration of Therapy
2000 Recommendation: The Panel suggests that, once initiated, IV bisphosphonates be continued until evidence of substantial decline in a patient's general performance status. The Panel stresses 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-related events (SREs).
2003 Recommendation: No change
Role in Control of Pain Secondary to Bone Metastases
2000 Recommendation: The Panel recommends that current standards of care for cancer pain, analgesics, and local radiation therapy should not be displaced by bisphosphonates. IV pamidronate is recommended in women with pain caused by osteolytic metastasis to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, because it was associated with a modest pain control benefit in controlled trials.
2003 Recommendation: The Panel recommends that the current standards of care for cancer pain management must be applied throughout bisphosphonate therapy and is required by good clinical practice. These standards of care for pain management include analgesics, corticosteroids, interventional procedures, nonsteroidal anti-inflammatory agents, systemic radiopharmaceuticals, and local radiation therapy. Among other therapeutic options, IV pamidronate or zoledronic acid may be of benefit among women with pain caused by bone metastases to relieve pain when used concurrently with systemic chemotherapy and/or hormonal therapy, because it was associated with a modest pain control benefit in controlled trials.
2000 Recommendation: There is insufficient evidence to support a role for IV bisphosphonates as an adjunctive therapy to radiation therapy in women with pain caused by metastatic bone disease when systemic chemotherapy and/or hormonal therapy is not being used. The role of bisphosphonates vis-a-vis radiation therapy as the sole therapy in this setting has not been determined. In women already being treated with local radiotherapy who have persistent or recurrent pain, bisphosphonates are an attractive but little-studied salvage therapy.
2003 Recommendation: No change
Role of Bisphosphonates With No Radiographic Evidence of Bone Metastases
Extraskeletal Metastases Without Evidence of Bone Metastases
2000 Recommendation: Starting bisphosphonates in women without evidence of bone metastases, even in the presence of other extraskeletal metastases, is not recommended. This clinical situation has not been studied using IV bisphosphonates and should be the focus of new clinical trials.
2003 Recommendation: No change
Bisphosphonates as Adjuvant Therapy
2000 Recommendation: Inconsistent, evolving data have been found in studies of bisphosphonate use in the adjuvant setting to prevent osseous metastases. Starting bisphosphonates in women at any stage of their nonosseous disease, outside of clinical trials, despite a high risk for future bone metastasis, is currently not recommended.
2003 Recommendation: No change
Bone Health In Women With A History Of Breast Cancer
Osteoporosis Prevention
2000 Recommendation: Oral bisphosphonates are one of several potential options that can be used for preservation of bone density in premenopausal women with treatment-induced (usually secondary to chemotherapy) menopause.
2003 Recommendation: Most women with newly diagnosed breast cancer are at risk of osteoporosis due to either their age or their breast cancer treatment. Oncology professionals, especially medical oncologists, need to take an expanded role in the routine and regular assessment of these women's bone health. The Panel recommended an algorithm for patient management to maintain bone health.
