scholarly journals The Role of Bisphosphonates in Breast Cancer

2003 ◽  
Vol 1 (2) ◽  
pp. 232-241 ◽  
Author(s):  
Richard L. Theriault
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Destruction ◽  
Standard Of Care ◽  
Cord Compression ◽  
Skeletal Metastases ◽  
Radiographic Appearance ◽  
Pathologic Fractures ◽  
Osteolytic Metastases ◽  
Microenvironmental Factors

Breast cancer frequently metastasizes to bone. Metastases result in skeletal morbidity including pathologic fractures, the need for radiation or surgery to bone, spinal cord compression and hypercalcemia. The pathophysiology of bone destruction is related to activation of osteoclasts by tumor-derived and bone marrow microenvironmental factors. One prominent osteoclast–activating factor associated with breast cancer is parathyroid hormone-related peptide (PTHrP). Bisphosphonates have been shown to impair osteoclast activity by decreasing recruitment from the monocyte macrophage cell line, inhibiting osteoclast function at the bone site and causing osteoclasts to undergo apoptosis. Clinical studies with bisphosphonates show an improvement in the control of hypercalcemia and a reduction in skeletal related morbidity with administration of pamidronate and zoledronic acid. Bisphosphonates have become the standard of care for osteolytic metastases associated with breast cancer. Recent data with zoledronic acid found that skeletal related morbidity may be reduced regardless of the radiographic picture of skeletal metastases. Thus, zoledronic acid may be valuable in osteolytic and osteoblastic disease as well as in disease with an osteolytic or osteoblastic radiographic appearance. In breast cancer with osteolytic disease, zoledronic acid may be more effective than pamidronate in reducing skeletal morbidity and prolonging the time to first skeletal event.

The use of Bisphosphonates in Patients with Breast Cancer

2002 ◽  
Vol 9 (6) ◽  
pp. 480-489 ◽  
Author(s):  
Catherine H. Van Poznak
Keyword(s):  
Breast Cancer ◽  
Spinal Cord ◽  
Randomized Clinical Trials ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Cord Compression ◽  
Bisphosphonate Therapy ◽  
Skeletal Metastases ◽  
Cancer Management ◽  
Pathologic Fractures

Background Bone is the most common site of breast cancer metastases. Skeletal metastases may be associated with harmful and painful events such as fractures, spinal cord compression, and hypercalcemia. By inhibiting osteoclasts and bone resorption, bisphosphonates can interrupt the process of bone destruction and decrease the risk of skeletal complications. Methods A review of the literature was undertaken regarding the use of bisphosphonates in breast cancer management, with particular attention to prospective, randomized clinical trials that have influenced the treatment of bone metastases. Results Large prospective, randomized trials have demonstrated that bisphosphonates are effective in reducing skeletal-related complications from metastatic breast cancer. Conclusions For many patients with osseous lesions from breast cancer, bisphosphonate therapy is a useful intervention in managing their disease. Bisphosphonates are the treatment of choice for hypercalcemia of malignancy and bisphosphonates reduce the risk of pathologic fractures, spinal cord compromise, the need for radiation or surgery to bone, and bone pain.

scholarly journals Cost-Effectiveness Analysis of Monthly Zoledronic Acid, Zoledronic Acid Every 3 Months, and Monthly Denosumab in Women With Breast Cancer and Skeletal Metastases: CALGB 70604 (Alliance)

2017 ◽  
Vol 35 (35) ◽  
pp. 3949-3955 ◽  
Author(s):  
Charles L. Shapiro ◽  
James P. Moriarty ◽  
Stacie Dusetzina ◽  
Andrew L. Himelstein ◽  
Jared C. Foster ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Zoledronic Acid ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Sensitivity Analyses ◽  
Skeletal Metastases ◽  
Quality Adjusted Life Years ◽  
Life Years ◽  
Quality Adjusted Life

Purpose Skeletal-related events (SREs) such as pathologic fracture, spinal cord compression, or the necessity for radiation or surgery to bone metastasis cause considerable morbidity, decrements in quality of life, and costs to the health care system. The results of a recent large randomized trial (Cancer and Leukemia Group B/Alliance for Clinical Trials in Oncology [CALGB/Alliance 70604]) showed that zoledronic acid (ZA) every 3 months was noninferior to monthly ZA in reducing the risks of SREs. We sought to determine the cost-effectiveness (CE) of monthly ZA, ZA every 3 months, and monthly denosumab in women with breast cancer and skeletal metastases. Methods Using a Markov model, costs per SRE avoided were calculated for the three treatments. Sensitivity analyses were performed where denosumab SRE probabilities were assumed to be 50%, 75%, and 90% lower than the ZA SRE probabilities. Quality-adjusted life-years were also calculated. The analysis was from the US payer perspective. Results The mean costs of the denosumab treatment strategy are nine-fold higher than generic ZA every 3 months. Quality-adjusted life-years were virtually identical in all the three treatment arms; hence, the optimal treatment would be ZA every 3 months because it was the least costly treatment. The sensitivity analyses showed that relative to ZA every 3 months, the incremental costs per mean SRE avoided for denosumab ranged from $162,918 to $347,655. Conclusion ZA every 3 months was more CE in reducing the risks of SRE than monthly denosumab. This analysis was one of the first to incorporate the costs of generic ZA and one of the first independent CE analyses not sponsored by either Novartis or Amgen, the makers of ZA and denosumab, respectively. ZA every 3 months is the more CE option and more reasonable alternative to monthly denosumab.

scholarly journals PTH1R-CaSR Cross Talk: New Treatment Options for Breast Cancer Osteolytic Bone Metastases

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Yanmei Yang ◽  
Bin Wang
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Treatment Options ◽  
Bone Destruction ◽  
Metastatic Breast ◽  
Tumor Burden ◽  
Skeletal Metastases ◽  
Vicious Cycle ◽  
Calcium Sensing ◽  
New Treatment

Metastatic breast cancer (BrCa) is currently incurable despite great improvements in treatment of primary BrCa. The incidence of skeletal metastases in advanced BrCa occurs up to 70%. Recent findings have established that the distribution of BrCa metastases to the skeleton is not a random process but due to the favorable microenvironment for tumor invasion and growth. The complex interplay among BrCa cells, stromal/osteoblastic cells, and osteoclasts in the osseous microenvironment creates a bone-tumor vicious cycle (a feed-forward loop) that results in excessive bone destruction and progressive tumor growth. Both the type 1 PTH receptor (PTH1R) and extracellular calcium-sensing receptor (CaSR) participate in the vicious cycle and influence the skeletal metastatic niche. Thus, this review focuses on how the PTH1R and CaSR signaling pathways interact and contribute to the pathogenesis of BrCa bone metastases. The effects of intermittent PTH and allosteric modulators of CaSR for the use of bone-anabolic agents and prevention of BrCa bone metastases constitute a proof of principle for therapeutic consideration. Understanding the interplay between PTH1R and CaSR signaling in the development of BrCa bone metastases could lead to a novel therapeutic approach to control both osteolysis and tumor burden in the bone.

scholarly journals Metastatic Bone Disease in Patients with Solid Tumors–-Burden of Bone Disease and the Role of Zoledronic Acid

2009 ◽  
Vol 1 ◽  
pp. CMT.S1958
Author(s):  
Vera Hirsh
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Bone Disease ◽  
Large Scale ◽  
Comparative Trial ◽  
Palliative Radiotherapy ◽  
Bone Lesions ◽  
Pathologic Fractures

Bisphosphonates have become an integral component of the therapeutic repertoire for cancer patients at risk for skeletal-related events (SREs) such as pathologic fractures, bone pain requiring palliative radiotherapy, the need for orthopedic surgery, spinal cord compression, and hypercalcemia of malignancy because of bone metastases. Administered via monthly 15-minute infusion of up to 4 mg (depending on creatinine clearance rate), zoledronic acid (ZOL) has been approved for preventing SREs in patients with bone metastases from any solid tumor or bone lesions from multiple myeloma. Although there have been limited head-to-head comparison trials between bisphosphonates, ZOL displayed benefits beyond pamidronate in a large-scale comparative trial in patients with bone metastases from breast cancer. Monitoring of serum creatinine levels and oral health is important to ensure safety and comfort during treatment. In addition to the established benefits of bisphosphonates in the advanced cancer setting, there is a strong preclinical rationale and emerging clinical evidence that ZOL has antitumor activities and can delay metastasis in patients with early breast cancer. Studies are underway in patients with other tumor types, and the role of bisphosphonates is likely to evolve.

Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study

2010 ◽  
Vol 28 (35) ◽  
pp. 5132-5139 ◽  
Author(s):  
Alison T. Stopeck ◽  
Allan Lipton ◽  
Jean-Jacques Body ◽  
Guenther G. Steger ◽  
Katia Tonkin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Metastases ◽  
Human Monoclonal Antibody ◽  
Randomized Study ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Osteonecrosis Of The Jaw ◽  
Double Blind Study ◽  
Double Blind

Purpose This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases. Patients and Methods Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression). Results Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39). Conclusion Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.

American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer

2003 ◽  
Vol 21 (21) ◽  
pp. 4042-4057 ◽  
Author(s):  
Bruce E. Hillner ◽  
James N. Ingle ◽  
Rowan T. Chlebowski ◽  
Julie Gralow ◽  
Gary C. Yee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Zoledronic Acid ◽  
Bone Health ◽  
Bone Destruction ◽  
Health Issues ◽  
Medical Oncologists ◽  
Intravenous Pamidronate ◽  
American Society ◽  
Osteoporosis Risk

Purpose: To update the 2000 ASCO guidelines on the role of bisphosphonates in women with breast cancer and address the subject of bone health in these women. Results: For patients with plain radiographic evidence of bone destruction, intravenous pamidronate 90 mg delivered over 2 hours or zoledronic acid 4 mg over 15 minutes every 3 to 4 weeks is recommended. There is insufficient evidence supporting the efficacy of one bisphosphonate over the other. Starting bisphosphonates in women who demonstrate bone destruction through imaging but who have normal plain radiographs is considered reasonable treatment. Starting bisphosphonates in women with only an abnormal bone scan but without evidence of bone destruction is not recommended. The presence or absence of bone pain should not be a factor in initiating bisphosphonates. In patients with a serum creatinine less than 3.0 mg/dL (265 μmol/L), no change in dosage, infusion time, or interval is required. Infusion times less than 2 hours with pamidronate or less than 15 minutes with zoledronic acid should be avoided. Creatinine should be monitored before each dose of either agent in accordance with US Food and Drug Administration (FDA) labeling. Oncology professionals, especially medical oncologists, need to take an expanded role in the routine and regular assessment of the osteoporosis risk in women with breast cancer. The panel recommends an algorithm for patient management to maintain bone health. Conclusion: Bisphosphonates provide a supportive, albeit expensive and non–life-prolonging, benefit to many patients with bone metastases. Current research is focusing on bisphosphonates as adjuvant therapy. Although new data addressing when to stop therapy, alternative doses or schedules for administration, and how to best coordinate bisphosphonates with other palliative therapies are needed, they are not currently being investigated.

Cost-Effectiveness of Denosumab Versus Zoledronic Acid in the Management of Skeletal Metastases Secondary to Breast Cancer

2012 ◽  
Vol 34 (6) ◽  
pp. 1334-1349 ◽  
Author(s):  
Sonya J. Snedecor ◽  
John A. Carter ◽  
Satyin Kaura ◽  
Marc F. Botteman
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Zoledronic Acid ◽  
Skeletal Metastases
Sign in / Sign up

Export Citation Format

Share Document