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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The results of available clinical studies suggest that breast cancer treatment significantly affect bone turnover, BMD and fracture risk. This is for instance the case for all third-generation aromatase inhibitors. For these reasons it is recommended that breast cancer patients exercise regularly and take daily calcium (1500 mg) and vitamin D (800UI) supplements. Most experts recommend that all women starting medical castration or aromatase inhibitor therapy should be assessed for their risk of osteoporosis and undergo bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry (DEXA). Patients with pre-existing osteopenia and osteoporosis should be evaluated for conditions which worsen skeletal health, such as vitamin D deficiency, hyperparathyroidism, hyperthyroidism and hyper-calcuria. If these patients have a BMD score of -2.5 or lower, a low BMD (T-score between -1 and -2.5) and additional risk factors for osteoporosis or fragility fractures, bisphosphonate therapy should be considered. The optimal duration of bisphosphonate therapy is unknown. It should probably be given for as long as aromatase inhibitor therapy is continued. In addition, bisphosphonate therapy may also reduce the risk of bone metastases. This approach seems to be cost effective based on an economic evaluation model.
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PMID:Risks of osteoporosis associated with breast cancer treatment: the need to access to preventive treatment. 1970 24

Although the incidence of breast cancer has increased, there is a concurrent decrease in the death rate, and the outlook for women with early-stage breast cancer remains positive. The current 5-year survival rate of women diagnosed with breast cancer is nearly 90%, due, in part, to the use of effective adjuvant therapies that often include aromatase inhibitors. However, long-term treatment with these therapies is known to have adverse effects on bone metabolism, leading to bone loss. Bone loss during adjuvant endocrine therapy may be higher than that observed during menopause and may require more potent therapy. Although there are approved treatments for osteolytic bone lesions from bone metastases, there is no approved therapy for bone loss associated with adjuvant cancer therapy. Bisphosphonates have demonstrated promising results in this setting, and zoledronic acid is currently under consideration by the US FDA and Europe (EMEA) for the treatment of aromatase inhibitor-associated bone loss.
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PMID:Managing aromatase inhibitor-associated bone loss in breast cancer. 1980 20

A 55-year old woman, who underwent left mastectomy (Bt+Ax), was revealed to have sternum metastasis by postoperative 99mTc bone scanning(T1bN1M1). She received daily aromatase inhibitor (anastrozole), as a primary systemic endocrine therapy, and biweekly pamidronate for metastatic breast cancer. However, she depended on folk medicine a year later, at which time the primary treatment was discontinued. Another year later, the bone metastases developed with increased serum levels of tumor markers (CEA, CA19-9, and NCC-ST-439). Then, she underwent three different regimens of systemic chemo-endocrine therapy over the following three years, including CAF+MPA as the first-line, paclitaxel (PTX) + anastrozole as the second-line, and S-1+anastrozole as the third-line regimen. She recently completed 10 courses of the fourth-line regimen[tri-weekly docetaxel (DOC) and high-dose toremifene (TOR 120 mg/day)], which reduced levels of 99mTc accumulation in the multiple bone metastases and levels of the serum tumor markers to the normal range. No severe adverse events occurred except peripheral thrombovasculitis (grade 2) in her left anterior arm during the fourth regimen. She recently maintains the current status by taking a regular dose (40 mg/day) of toremifene for 5 months. Combination treatment with DOC and high-dose TOR can be one of the worthwhile regimens as systemic chemo-endocrine therapy for patients with advanced breast cancer who develop bone metastases.
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PMID:[A case of advanced breast cancer with multiple bone metastases responding to docetaxel and high-dose toremifene as fourth-line chemo-endocrine therapy]. 2000 68

Aromatase inhibitors have largely replaced tamoxifen as the first-line treatment for postmenopausal women with metastatic, hormone receptor-positive (HR+) breast cancer. However, many patients develop clinical resistance with prolonged treatment, and oestrogen deprivation following aromatase inhibition can result in loss of bone mineral density. Furthermore, most patients with metastatic breast cancer develop bone metastases, and the resulting adverse skeletal-related events are a significant cause of patient morbidity. Src, a non-receptor tyrosine kinase, is a component of signalling pathways that regulate breast cancer cell proliferation, invasion and metastasis as well as osteoclast-mediated bone turnover. Preclinical evidence also suggests a role for Src in acquired endocrine resistance. As such, Src inhibition represents a logical strategy for the treatment of metastatic breast cancer. In vitro, combination therapy with Src inhibitors and endocrine agents, including aromatase inhibitors, has been shown to inhibit the proliferation and metastasis of both endocrine-responsive and endocrine-resistant breast cancer cell lines more effectively than either of the therapy alone. Src inhibition has also been shown to suppress osteoclast formation and activity. Combination therapy with aromatase inhibitors and Src inhibitors therefore represents a novel approach through which the development of both acquired resistance and bone pathology could be delayed. Data from clinical trials utilising such combinations will reveal if this strategy has the potential to improve patient outcomes.
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PMID:Combining Src inhibitors and aromatase inhibitors: a novel strategy for overcoming endocrine resistance and bone loss. 2047 23

We report a case of multi-drug-resistant breast cancer with liver metastases which completely responded and improved the quality of life (QOL)by S-1 monotherapy. The patient was a 53-year-old woman, who was diagnosed as breast cancer with invasive chest wall, cervical lymph node metastases, multiple bone metastases and bilateral pleural effusion[invasive ductal carcinoma, scirrhous type, ER(-), PgR(+), HER2(1+)]. After six courses of cyclophosphamide+epirubicin(CE)and weekly paclitaxel for 3 months, cervical lymph node metastasis was judged as a partial response(PR)and the bilateral pleural effusion disappeared. After chemotherapy, aromatase inhibitor (AI) was used. However, primary lesion and multiple bone metastases no change(NC). Following pass through AI+ oral anticancer drug combination chemotherapy and oral anticancer drug monotherapy, the therapy was changed to palliative, and she was referred to our hospital in January 2007. On arrival at the hospital, respiratory distress and bilateral pleural effusion had appeared, so it was an emergency admission. After removing the pleural effusion, pleurodesis was done and the symptoms disappeared. Although AI plus bisphosphonate therapy were started at hospital discharge, disease progression and fatigue appeared. In December 2007, we started S-1 monotherapy. S-1 was given orally at 80 mg/m2 for day 1-28 followed by a 2-week rest period, within a 6-week courses. Six months after treatment was started, multiple liver metastases disappeared and peritoneal effusion decreased. During the period of S-1 treatment, there were no serious adverse events, and treatment was possible without compromising QOL. This result suggested that S-1 treatment was a reasonable option for multi-drug-resistant breast cancer.
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PMID:[A case of multi-drug resistant breast cancer with liver metastasis treated effectively by S-1 monotherapy]. 2116 Feb 66

Bone metastases result in considerable morbidity, often affecting quality of life and independence over years, and may place complex demands on health care resources. The bisphosphonates have been shown to reduce skeletal morbidity in multiple myeloma and solid tumours affecting bone by 30-50%. Quite appropriately, these agents are increasingly used alongside anticancer treatments to prevent skeletal complications and relieve bone pain. The use of bisphosphonates in early cancer has become increasingly important to prevent adverse effects of cancer treatments on bone health. These include chemotherapy induced ovarian failure and the use of aromatase inhibitors in breast cancer and androgen deprivation therapy in prostate cancer. Bisphosphonate strategies, similar to those used to treat post-menopausal osteoporosis, are the intervention of choice for patients with low bone mineral density or rapid bone loss, along with adequate calcium and vitamin D intake and a healthy lifestyle. There is a strong preclinical rationale for bisphosphonates to prevent metastasis, primarily through inhibition of the vicious cycle of metastasis within the microenvironment. Recent data suggest that adjuvant bisphosphonates, at least in some patient subgroups, may modify the course of the disease and disrupt the metastatic process, reducing the risks of disease recurrence. In comparison to most other cancer treatments, adverse events related to bisphosphonate therapy are generally mild and infrequent; thus, the benefits of treatment within licensed indications will almost always outweigh the risks.
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PMID:Bisphosphonates in oncology. 2132 Jun 52

Breast cancer is the most frequently diagnosed and second deadliest cancer among women. Bisphosphonates are stable pyrophosphate analogues used to treat skeletal-related events resulting from bone metastases. In the adjuvant setting, they have been shown to prevent aromatase inhibitor-associated and chemotherapy-induced bone loss. There is a growing body of evidence that bisphosphonates have direct and indirect anticancer activity in the preclinical and clinical settings. These include the inhibition of tumor growth; induction of apoptosis; synergism with chemotherapy; inhibition of tumor migration, invasion, and metastasis; reduction in disseminated tumor cells; inhibition of angiogenesis; stimulation of immune surveillance; and suppression of bone-derived growth factors. In addition to reducing the risk of breast cancer, bisphosphonate therapy has been shown to improve outcomes of early and metastatic breast cancer treatment. This review provides a brief overview of the current role of bisphosphonates in clinical practice and discusses their potential as anticancer agents.
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PMID:Bisphosphonates in breast cancer: clinical activity and implications of preclinical data. 2147 25

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

Breast cancer and bone health are closely linked. Early menopause induced by gonadotropin-releasing hormone analogues or chemotherapy as well as aromatase inhibitors reduce oestrogen levels, thereby causing cancer treatment-induced bone loss (CTIBL). Furthermore, bone metastases are commonly found in advanced disease. Current treatment options for bone lesions comprise systemic anti-tumour therapy, irradiation, surgery and bisphosphonates. The main mechanism of osteolysis, osteoclast activation, is induced by the RANK ligand and suppressed by osteoprotegerin (OPG). A human antibody targeting the RANK ligand, denosumab, had superior activity compared to OPG and was therefore further developed in the clinical setting. This article reviews clinical data on denosumab. Data were obtained by searching the Medline database and abstracts from the ASCO annual meeting, ASCO breast meeting, ECCO, ESMO, and the San Antonio Breast Cancer Symposium. Clinical trials have demonstrated that denosumab reduces markers of bone turnover, and suggest equal efficacy to bisphosphonates in reducing the rate of skeletal-related events. While overall fewer side effects were observed, a numerically increased rate of osteonecrosis of the jaw was reported. Denosumab was well tolerated, and clinical activity was similar to bisphosphonates in metastatic disease. Trials of denosumab in the prevention of CTIBL are ongoing.
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PMID:Breast Cancer: Rank Ligand Inhibition. 2177 14

Osteonecrosis of the jaw (ONJ) is a serious side effect in patients receiving intravenous nitrogen-containing bisphosphonates (B). It has also been reported to occur due to oral administration of B. Most cases will appear after receiving B for more than 1 year. The authors report a case of a 67-year-old woman with osteoporosis who had received oral alendronate sodium for 2 years and stopped the treatment due to dyspepsia. 18 months later she was diagnosed with breast cancer and bone metastases. She started a treatment based on aromatase inhibitors and zoledronic acid (Z). She developed ONJ soon after the third administration. She was treated with antibiotics, anti-inflammatories and a chlorexidine colutory. She recovered 3 months later. ONJ secondary to Z may occur also earlier than it was thought in patients with a history of taking oral B.
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PMID:Early appearance of osteonecrosis of the jaw after zoledronic acid in a patient with a long history of taking oral bisphosphonates. 2260 20


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