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)

Hypercalcemia of malignancy carries an extremely grim prognosis. The most common mechanism underlying hypercalcemia of malignancy is production by the tumor cells of cytokines responsible for osteoclastic differentiation and, therefore, lysis of the bone adjacent to the tumor. A minority of cases are attributable to increased renal reabsorption of calcium caused by a humoral factor, termed parathyroid hormone-related peptide, which is produced by some primary tumors. These two mechanisms can be involved in conjunction, particularly in patients with breast cancer. The development of osteolytic metastases initiates a vicious cycle in which bone degradation products, especially growth factors, stimulate the growth of the tumor cells located at the bone-tumor interface. Parathyroid hormone-related peptide is produced by many malignant tumors, most notably those of the breast. In addition to its endocrine effect on the kidney, it may have a paracrine effect consisting of enhancement of osteoclastic differentiation with osteolysis of the bone adjacent to the tumor. Other factors produced by primary tumor cells, such as proteases, intercellular adhesion molecules, or bone matrix proteins, may influence the propensity for the tumor to produce bone metastases. Bisphosphonates are usually effective in inducing a remission of hypercalcemia of malignancy and in improving the clinical manifestations of osteolytic metastases. Elucidation of the factors that influence the propensity for malignancies to metastasize to bone would improve our ability to use bisphosphonates optimally as adjuncts to tumor therapy.
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PMID:Role of Parathyroid Hormone Related Peptide (PTHrP) in Hypercalcemia of Malignancy and the Development of Osteolytic Metastases. 1907 66

Cancer and its treatment can compromise bone health, leading to fracture, pain, loss of mobility, and hypercalcemia of malignancy. Bone metastasis occurs frequently in advanced prostate and breast cancers, and bony manifestations are commonplace in multiple myeloma. Osteoporosis and osteopenia may be consequences of androgen-deprivation therapy for prostate cancer, aromatase inhibition for breast cancer, or chemotherapy-induced ovarian failure. Osteoporotic bone loss and bone metastasis ultimately share a pathophysiologic pathway that stimulates bone resorption by increasing the formation and activity of osteoclasts. Important mediators of pathologic bone metabolism include substances produced by osteoblasts, such as RANKL, the receptor activator of nuclear factor kappa B ligand, which spurs osteoclast differentiation from myeloid cells. Available therapies are targeted to various steps in cascade of bone metastasis.
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PMID:The science and practice of bone health in oncology: managing bone loss and metastasis in patients with solid tumors. 1987 35

Bisphosphonates are the standard of care for preventing skeletal morbidity and treating hypercalcemia of malignancy in patients with bone metastases. Zoledronic acid (intravenous; 4 mg monthly) is approved to prevent skeletal-related events (SREs) in patients with bone metastases from several tumor types, and can improve survival in some subsets of patients with skeletal metastases and high baseline bone turnover. In the adjuvant setting, bisphosphonates have shown clinical efficacy for preventing cancer treatment-induced bone loss and promise for reducing disease recurrence. For example, early studies of clodronate showed the potential for bisphosphonates to prevent bone metastases and prolong survival, but results with clodronate have been inconsistent. Recently, the more active bisphosphonate zoledronic acid (4 mg every 6 months) prevented bone loss and significantly reduced the risk of disease-free survival events by 36% (P = .01) compared with adjuvant endocrine therapy alone in a large phase III trial (N = 1,803) in premenopausal women with early breast cancer. Notably, these benefits were not limited to bone, because the addition of zoledronic acid reduced disease recurrence at all sites. Similarly, twice-yearly zoledronic acid has reduced disease recurrence in large phase III trials in more than 1,600 postmenopausal women with early breast cancer. Several ongoing trials (involving more than 20,000 patients altogether) are evaluating the efficacy of bisphosphonates for prevention of metastases in breast, prostate, and lung cancers; and multiple myeloma. Results from these studies are likely to expand the role of bisphosphonates, especially zoledronic acid, in the adjuvant therapy setting.
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PMID:Bisphosphonates in the prevention of disease recurrence: current results and ongoing trials. 2002 70

Malignancy-associated hypercalcemia is one of the commonest causes of hypercalcemia. Clinically, it has been subdivided into HHM (humoral hypercelcemia of malignancy) and LOH (local osteolytic hypercalcemia) . PTHrP (PTH related protein) , which has high homology with PTH in its N-terminus and binds to a common receptor (PTH1R) with PTH, plays a central role in the development of hypercalcemia in HHM. Although most features of HHM can be explained by excessive action of circulating PTHrP, decreased serum level of 1,25 (OH) (2)D and markedly suppressed bone formation found in HHM cannot be explained by the action of N-terminus of PTHrP. Fragments of PTHrP that do not bind to PTH1R, found in the circulation of HHM patients, or some other cytokines secreted by cancer cells may modify the clinical features of HHM. PTHrP also plays important roles in the development of LOH in some cancers, such as breast cancer. In this article, the role of cytokines, mainly PTHrP, in MAH will be reviewed.
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PMID:[Cytokines in bone diseases. Cytokines and malignancy-associated hypercalcemia]. 2089 31

Bone metastases add to the burden of breast cancer, with patients experiencing severe bone pain, pathologic fractures, spinal cord compression, and hypercalcemia of malignancy. Nitrogen-containing bisphosphonates have become the standard treatment for skeletal-related events and bone pain, as well as for bone loss associated with chemotherapy and aromatase inhibitors. Emerging preclinical and clinical evidence indicates that bisphosphonates negatively affect multiple processes that support tumor growth and proliferation and formation of metastases. Several small clinical trials suggest that bisphosphonates can modify angiogenic factors, immune surveillance, and disseminated tumor cells detected in bone marrow. Emerging data suggest that bisphosphonates used for osteoporosis prevention may inhibit breast cancer development. Three large prospective studies have shown improved outcomes with the addition of zoledronic acid to conventional neoadjuvant or adjuvant therapy. This article focuses on current clinical trials examining the use of bisphosphonates in patients with breast cancer.
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PMID:Bisphosphonates in breast cancer: antitumor effects. 2155 88

Zoledronic acid (ZOL) is a new generation bisphosphonate with improved efficacy benefits over pamidronate in preclinical testing. In addition, ZOL is superior to pamidronate in the treatment of hypercalcemia of malignancy. ZOL is also the first bisphosphonate to demonstrate efficacy in patients with bone metastases from solid tumors other than breast cancer, such as prostate cancer. In this study, we investigated ZOL treatment in 17 Japanese men with advanced prostate cancer, treated at the Aichi Medical University Hospital between August 2006 and November 2007. The 17 patients had biopsy-confirmed prostate cancer and were found to harbor bone metastasis upon bone scintigraphy. ZOL was administered intravenously at a dose of 4 mg over 15 min every 4 weeks. ZOL was well tolerated with mild renal dysfunction in 2 patients (11.8%), while 1 patient (5.8%) developed skin rash. No significant side effects were observed. Subjective improvement in bone pain was reported in 14 patients (32.4%). ZOL, therefore, is a safe and effective drug that remains an important component of the urologist's armamentarium against advanced prostate cancer.
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PMID:The use of zoledronic acid in Japanese men with stage D2 prostate cancer. 2296 48

Bisphosphonates are osteoclast inhibitors, currently being used in oncology to prevent or delay bone morbidity in cancer. Oral and intravenous formulations of bisphosphonates have been found to be efficacious in preventing skeletal-related events such as bone pain, pathologic fractures, spinal cord compression and hypercalcemia of malignancy, in patients with bone metastatic breast cancer. Bisphosphonates are also used to prevent bone loss associated with anti-estrogen therapy using aromatase inhibitors. In addition to its role in preventing bone resorption, several pre-clinical studies have noted an anti-tumor role as well. Recent research effort has particularly focused on investigating an adjuvant role for bisphosphonates in early breast cancer. Recently, few randomized trials have found a beneficial effect for adjuvant use of the aminobisphosphonate, zoledronate, in older patients who are post-menopausal. This review article will summarize the various clinical studies investigating the role of bisphosphonates in breast cancer.
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PMID:Bisphosphonates in breast cancer. 2482 52

Hypercalcaemia of malignancy (HCM) is a grave emergency in a cancer patient. Metastatic breast cancer and multiple myeloma are two of its important causes. Moreover, breast cancer is a predisposing factor for secondary malignancy, multiple myeloma being one of them. We report an interesting case of HCM in which we labelled the first two admissions to metastatic breast cancer. However, on third admission again for HCM, we diagnosed a coexisting multiple myeloma. As early diagnosis is the crux to decrease morbidity and prolong survival in HCM, this case emphasises the fact that more than one malignant cause can exist in the same patient.
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PMID:Hypercalcaemia of malignancy: two primaries in the same patient. 2496 87

Bone is the most common site of distant metastases in breast cancer that can cause severe and debilitating skeletal related events (SRE) including hypercalcemia of malignancy, pathologic fracture, spinal cord compression and the need for palliative radiation therapy or surgery to the bone. SRE are associated with substantial pain and morbidity leading to frequent hospitalization, impaired quality of life and poor prognosis. The past 25 years of research on the pathophysiology of bone metastases led to the development of highly effective treatment options to delay or prevent osseous metastases and SRE. Management of bone metastases has become an integral part of cancer treatment requiring expertise of multidisciplinary teams of medical and radiation oncologists, surgeons and radiologists in order to find an optimal treatment for each individual patient. A group of international breast cancer experts attended a Skeletal Care Academy Meeting in November 2012 in Istanbul and discussed current preventive measures and treatment options of SRE, which are summarized in this evidence-based consensus for qualified decision- making in clinical practice.
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PMID:Bone health in breast cancer patients: a comprehensive statement by CECOG/SAKK Intergroup. 2498 66

The long-term effects of many drugs are unknown. Established risks are communicated to patients who participate in clinical trials during the informed consent process. However, unknown and unanticipated side effects of medications may occur years after treatment. Patients with metastatic bone cancer experience an imbalance between tumor cells and the bone marrow microenvironment. Increased cytokine release, osteoclastic activity, and uncoupled osteoblastic activity lead to weakened bone structure and osteolytic lesions. The bisphosphonates are a class of drugs available in IV and oral formulations to treat and prevent bone loss and decrease the risk of skeletal-related events. Intravenous bisphosphonates such as zoledronic acid and pamidronate disodium are approved by the US Food and Drug Administration for the treatment of bone pain and hypercalcemia of malignancy and the prevention of painful bone fractures in patients with metastatic bone cancer. Oral bisphosphonates such as alendronate, risedronate, and etidronate are used to reduce the risk of skeletal fractures in patients with osteoporosis and in breast cancer. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a rare but painful complication of treatment characterized by infection, exposed bone, and poor wound healing. In this article, we discuss BRONJ and identify past, present, and future ethical and legal issues surrounding bisphosphonate administration.
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PMID:Bisphosphonate-related osteonecrosis of the jaw: historical, ethical, and legal issues associated with prescribing. 2503 78


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