Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parathyroid-hormone-related-peptide (PTHrP) has been shown to be important in the pathogenesis of hypercalcemia of malignancy. The malignancies most commonly associated with hypersecretion of PTHrP include squamous cell carcinoma and breast cancer. The pathogenesis of hypercalcemia associated with hepatocellular carcinoma was evaluated in this study. Two male patients with hepatocellular carcinoma were found to have severe hypercalcemia at initial presentation. PTHrP was measured with radioimmunoassay in these two patients before treatment as well as in nine other patients with hepatocellular carcinoma but without hypercalcemia. The levels were markedly elevated in the two patients with hypercalcemia (29.3 and 32.1 pM), but were less than 5 pM in the nine patients without hypercalcemia. These results suggest that PTHrP was important in the pathogenesis of hypercalcemia associated with hepatocellular carcinoma in these men.
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PMID:Humoral hypercalcemia of hepatocellular carcinoma associated with elevated levels of parathyroid-hormone-related-peptide. 1525 88

Bone is a preferred site of metastasis for many solid tumors, and the complications associated with bone metastases can result in significant skeletal morbidity including severe bone pain, pathologic fracture, spinal cord compression, and hypercalcemia of malignancy (HCM). Bisphosphonates are the current standard of care for preventing skeletal complications associated with bone metastases. Clinical trials investigating the benefit of bisphosphonate therapy have used a composite end point defined as a skeletal-related event (SRE) or bone event, which typically includes pathologic fracture, spinal cord compression, radiation or surgery to bone, and HCM. Bisphosphonates have been shown to significantly reduce the incidence of these events in patients with bone metastases. Zoledronic acid (Zometa; Novartis Pharmaceuticals Corp.; East Hanover, NJ), pamidronate (Aredia; Novartis Pharmaceuticals Corp.), clodronate (Bonefos; Anthra Pharmaceuticals; Princeton, NJ), and ibandronate (Bondronat; Hoffmann-La Roche Inc.; Nutley, NJ) all have demonstrated efficacy superior to that of placebo in patients with breast cancer. Zoledronic acid is the only bisphosphonate that has been compared directly with pamidronate, and it was shown by multiple event analysis to be significantly more effective at reducing the risk of an SRE. In patients with prostate cancer, clodronate, etidronate (Didronel; Procter and Gamble Pharmaceuticals, Inc.; Cincinnati, OH), and pamidronate have demonstrated transient palliation of bone pain. However, zoledronic acid is the only bisphosphonate to demonstrate both significant and sustained pain reduction and a significantly lower incidence and longer time to onset of SREs compared with placebo. Zoledronic acid is also the only bisphosphonate to demonstrate efficacy in patients with bone metastases from a variety of other solid tumors, including lung cancer and renal cell carcinoma. In conclusion, bisphosphonates effectively reduce skeletal complications in patients with bone metastases from breast cancer, and zoledronic acid has demonstrated the broadest clinical activity in patients with a wide variety of tumor types.
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PMID:Bisphosphonates: clinical experience. 1545 26

Patients with advanced breast cancer who develop bone metastases suffer an ongoing risk of skeletal complications that can have a significant impact on their quality of life (QoL). These complications include bone pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy (HCM), a potentially life-threatening condition. Treatment options include radiotherapy to palliate bone pain and/or prevent impending fracture, orthopedic surgery to prevent or repair fractures, analgesics, and bisphosphonates, which can significantly reduce the risk of skeletal complications and delay their onset. Of the known bisphosphonates, zoledronic acid is the most potent. Since its regulatory approval in the United States and Europe in 2001, zoledronic acid (4 mg by 15-minute infusion) has become widely used and has replaced pamidronate (90 mg by 2-hour infusion) as the standard of care for treating bone metastases from breast cancer and bone lesions from multiple myeloma. Zoledronic acid has also demonstrated significant long-term benefits in randomized trials in prostate cancer and other solid tumors, whereas other bisphosphonates have failed. In long-term, phase III clinical testing, zoledronic acid provided significant treatment benefits beyond those of pamidronate in patients with breast cancer and demonstrated a safety profile comparable with pamidronate. Therefore, zoledronic acid is now recommended from the first diagnosis of bone metastasis. Other intravenous bisphosphonates include clodronate and ibandronate. Both are approved in Europe, but their efficacy relative to pamidronate and zoledronic acid is not known.
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PMID:Management of bone metastases in breast cancer. 1571 97

Deterioration of bone health is a major concern during progression and treatment of patients with breast cancer, especially in postmenopausal women. Disease- and treatment-associated skeletal-related events include fractures, spinal compression, bone pain, and hypercalcemia of malignancy. Bisphosphonates, which inhibit osteoclastic bone resorption, are important new agents in the management of skeletal-related events, and their impact on breast cancer-related bone metastases and on bone loss during long-term estrogen deprivation therapies such as aromatase inhibitors is reviewed. Intravenous pamidronate has become the standard bisphosphonate to reduce or delay skeletal complications of advanced breast cancer bone metastases, but the more potent agent, zoledronic acid, appears to be at least as effective. Another agent, ibandronate, is also active but has not been investigated in comparison with the other intravenous bisphosphonates. Zoledronic acid is the most convenient to administer, requiring only a short infusion. The effects of bisphosphonates on bone health in women with early breast cancer are also being investigated. A single yearly infusion of zoledronic acid has been shown to significantly increase bone mineral density in osteoporotic postmenopausal women and to reduce biochemical markers of bone turnover. The possibility of such treatment-reversing aromatase inhibitor-associated bone loss during adjuvant therapy of breast cancer is being evaluated in a trial of letrozole, with zoledronic acid added initially or after the onset of bone loss or fracture.
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PMID:Optimizing bisphosphonate therapy in patients with breast cancer on endocrine therapy. 1571 98

Bone metastases commonly occur in the course of malignant tumor disease. For many years, attempts have been made to identify factors for the management of cancer-induced skeletal complications. Nowadays, synthetic antiresorptive agents are considered to be indispensable for the treatment of cancer-related skeletal events, such as bone metastasis. The most common of these drugs are the bisphosphonates, which represent one of the most significant advances over the last 10 years in the field of supportive care and cancer. They are used for the treatment of cancer-induced hypercalcemia, for the prevention and treatment of postmenopausal osteoporosis, for patients with bone metastases secondary to breast cancer and multiple myeloma. A third-generation bisphosphonate, zolendronate, has been shown to minimize the destructive consequences of bone metastases and to exert a profound effect on tumor-induced osteolysis and tumor growth in bone. Zoledronate is already used for the treatment of hypercalcemia of malignancy, multiple myeloma-related osteolytic events and for patients with documented bone metastases from solid tumors in conjunction with standard antineoplastic therapy. The structure-function activity of the three generations of bisphosphonates developed to date, the in vitro models used for studying their effects on osteoclasts and osteoblasts, as well as the results of clinical trials obtained by the third generation bisphosphonate, zoledronic acid, are presented.
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PMID:In vitro and in vivo antiresorptive effects of bisphosphonates in metastatic bone disease. 1579 91

Biophosphonates are analogues of pyrophosphate. The mechanism of action of bisphosphates is the inhibition of osteoclast activation (antiresorptive mechanism). The oral bioavailability of biophosphonates is only about 1-2%, and because of gastrointestinal side effects (mainly esophageal irritation), oral agents are less useful in oncology. Biophosphonates are used for the treatment of Paget s disease of bone, the prevention of osteoporosis, and in another clinical scenarios as the prevention of bone disease after organ transplantation. In clinical oncology biophosphonates are used for the treatment of hypercalcemia of malignancy, prevention and treatment of bone events related to bone metastases, and in the prevention of osteoporosis related to breast cancer. According to American Society of Clinical Oncology (ACO) guidelines, biophosphonates should be used in hypercalcemia of malignancy and bone events related to metastases of breast cancer and multiple myeloma.
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PMID:[Biphosphonates in oncology]. 1645 91

Bone metastases are a common occurrence in patients with breast cancer, lung cancer and prostate cancer. Bone metastases cause considerable morbidity including pain, impaired mobility, pathologic fracture, spinal cord or nerve root compression, bone marrow infiltration and hypercalcemia of malignancy. These complications result from the derangement of normal bone metabolism that arise from interactions between factors originating in tumor cells and others originating in the microenvironment of the bone. Fortunately, there is an increasing array of treatment options for the skeletal complications associated with bone metastases arising from breast, lung, and prostate cancer. The goals of treatment for such skeletal complications are to relieve pain and reduce the risk of fracture. Traditional therapies to treat skeletal malignancies include radiation, surgery, and chemotherapy. In recent years, bisphosphonates have become the treatment of choice because of their ability to reduce bone resorption, leading to decreases in hypercalcemia, new osteolytic lesions, and fractures, thereby ameliorating pain and improving quality of life.
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PMID:Managing bone complications of solid tumors. 1696 20

Intervenous (IV) bisphosphonates are used for cancer patients with hypercalcemia of malignancy (HCM) and breast cancer bone metastases (BM). Recently, zoledronic acid, the most potent third generation bisphosphonate, has been approved for both HCM and BM of broad tumors. It showed 850-fold stronger activity than pamidronate in bone resorption assay, and clinical efficacy against multiple cancer bone lesion has been confirmed in randomized clinical trials. Zoledronic acid becomes one of the most used bisphosphonate for cancer patients in the world, and the results of clinical trials for cancer treatment-induced bone loss or postmenopausal osteoporosis are now updating.
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PMID:[Therapeutic agents for disorders of bone and calcium metabolism: Zoledronic acid]. 1721 Oct 90

Bisphosphonates are effective inhibitors of osteoclast activity and bone resorption, and are standard treatments for osteoporosis, hypercalcemia of malignancy, and metabolic bone disease. Bisphosphonates have also been established to effectively reduce skeletal-related events due to malignancy metastatic to bone. Bisphosphonates are now being incorporated into breast cancer treatment regimens in order to combat osteoporosis caused by ovarian suppression, chemotherapy treatment, aromatase inhibitors and the postmenopausal state itself. A large body of evidence suggests that African-American women are at higher risk for osteoporosis-related morbidity than their Caucasian counterparts. In this review, we highlight recommendations toward screening for osteoporosis in high-risk populations. We summarize the mechanisms of action of bisphosphonates in the treatment of osteoporosis and then summarize national recommendations toward incorporating the use of bisphosphonates as support for the bone health of breast cancer patients, as well as patients at high risk for osteoporosis.
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PMID:Bisphosphonate therapy for women with breast cancer and at high risk for osteoporosis. 1730 67

Bisphosphonates as a group of drugs were introduced for the management of various conditions such as osteoporosis, Paget's disease, multiple myeloma, hypercalcemia of malignancy, breast cancer, prostate cancer, and other tumors. This group of drugs has improved the quality of life in many patients with proven efficacy in limiting pain and skeletal-related events. The controversy of osteonecrosis of the jaws and bisphosphonates is a recent and growing problem. Osteonecrosis of the jaws is recognized as a serious complication of bisphosphonate therapy, more commonly with the intravenous form of the drugs. However, there is limited scientific understanding about the association between osteonecrosis of the jaws and bisphosphonates. In the present article we discuss various mechanisms of action of bisphosphonates, the rationale for occurrence of osteonecrosis in the jaws, and treatment guidelines for the condition.
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PMID:Bisphosphonates and osteonecrosis of the jaws: science and rationale. 1744 9


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