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

The detection of specific hormone receptors in normal and tumor tissue has brought new insight into the mechanisms of action of hormones and anti-hormones. The Swiss Cooperative Cancer Study Group (SAKK) has evaluated the antitumor effect of the new antiestrogenic substance tamoxifen in metastatic breast cancer. 158 postmenopausal patients treated with 20 mg/d tamoxifen by mouth are evaluable at present time. Complete and good partial remissions were achieved in 39 patients (25%) largely with soft tissue but also lung and bone metastases. Tamoxifen was well tolerated and caused few serious complications such as thrombosis/pulmonary embolism and hypercalcemia. These results confirm already published experience with tamoxifen, which may replace the estrogens as the primary endocrine treatment in postmenopausal mammary carcinoma metastasizing to soft tissues, lung and bone.
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PMID:[Antiestrogens: a new endocrine treatment possibility in metastasizing breast neoplasms. Experiences of the Swiss Cooperative Cancer Study Group with tamoxifen]. 69 81

Brain metastasis is one of the most critical metastatic lesion on the treatment of breast cancer. We reported a case with brain metastasis from breast cancer responding to chemoendocrine therapy. The patient was 71 years old female complaining gait disturbance. Solitary brain metastasis and multiple bone metastases of breast cancer were diagnosed by CT scan and bone scintigram. Standard radical mastectomy was done. Estrogen receptor was proved to be positive in both of the tumor and metastatic lymph node. Tamoxifen and UFT were administered as chemoendocrine therapy. Complete response of brain metastasis was recognized in CT scan and gait disturbance was complete recovered two months after the treatment. She is now living well.
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PMID:[A case of brain metastasis from breast cancer responding to chemoendocrine therapy]. 217 48

1,25-Dihydroxyvitamin D3 (1,25-(OH)2D3) has been shown to inhibit breast cancer cell growth both in vitro and in vivo. A major drawback is that high doses of 1,25-(OH)2D3 are needed which may result in undesirable side effects like the development of hypercalcemia and an increased risk of bone metastases due to the stimulation of bone resorption by 1,25-(OH)2D3. Several newly developed 1,25-(OH)2D3 analogs have a reduced calcemic activity, but their direct effects on bone resorption have not yet been examined. Presently, the antiestrogen tamoxifen is the most important endocrine therapy for breast cancer. Recent studies have demonstrated the benefit of the combination tamoxifen and 1,25-(OH)2D3/analogs for the inhibition of breast cancer cell growth. Besides inhibition of breast cancer growth tamoxifen appeared to have beneficial effects on bone. The purpose of the present study was to investigate the effect of tamoxifen on 1,25-(OH)2D3- and analogs (EB1089 and KH1060)-stimulated bone resorption in an in vitro model. Bone resorption was stimulated by 1,25-(OH)2D3 and analogs in a dose-dependent manner with KH1060 and EB1089 being more potent and 1,25-(OH)2D3. Tamoxifen caused a strong dose-dependent inhibition (70% at 10 microM) of 1,25-(OH)2D3- and EB1089-stimulated bone resorption. KH1060-stimulated bone resorption was also inhibited by tamoxifen but to a lesser extent (36%). Also the pure antiestrogen ICI164,384 but not 17 beta-estradiol inhibited 1,25-(OH)2D3-stimulated bone resorption. Together, this study demonstrates that tamoxifen considerably reduces 1,25-(OH)2D3/analogs-stimulated bone resorption and therefore may be useful to reduce the risk of bone metastases. This together with the observed beneficial effects on breast cancer cell growth indicates that tamoxifen together with 1,25-(OH)2D3/analogs is an interesting combination for the treatment of breast cancer. The mechanism of the bone resorption inhibitory action is not yet known but seems to be independent of the estrogen pathway.
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PMID:Antiestrogens inhibit in vitro bone resorption stimulated by 1,25-dihydroxyvitamin D3 and the vitamin D3 analogs EB1089 and KH1060. 783 15

Treatment for advanced breast cancer is not yet curative but aims to palliate the disease to make life as symptom free and as active for as long as possible with the minimum of adverse effects of treatment. The high prevalence and often long time course of the disease leads breast cancer to make major demands on health care resources. Radiotherapy is valuable for localized lesions, but more widespread disease relies on systemic treatment. Tamoxifen is the main agent for endocrine therapy, although aromatase inhibitors and progestogens are also important. Improvements in cytotoxic chemotherapy have come as much from methods to reduce toxicity as from new agents. Intensive chemotherapy with bone marrow support has not found a routine place in advanced breast cancer, but experience gained may have more application in the adjuvant treatment of high risk operable disease. Incorporation of quality of life measures is being increasingly recognized as essential for the proper evaluation of response to treatment. Although postoperative adjuvant systemic therapy now has an established place for early breast cancer, subsequent relapse responds less well to either endocrine or cytotoxic agents. Bone metastases are a major problem in advanced breast cancer, most of the damage being mediated by the stimulation of osteoclasts by tumour derived cytokines. Important advances in treatment have come from the use of bisphosphonates and beta emitting isotopes. Monitoring of bone metastases is enhanced by using biochemical parameters of response in addition to imaging techniques.
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PMID:Improving treatment for advanced breast cancer. 801 92

Adjuvant systemic treatments have greatly improved the prognosis of women with early breast cancer. Combination chemotherapy and, for patients with oestrogen receptor-positive (ER+) tumours, endocrine treatment has been found to reduce the frequency of relapse and improve survival. New adjuvant strategies include the introduction of taxanes into adjuvant chemotherapy schedules, the use of aromatase inhibitors in place of, or in addition to, tamoxifen, and the use of adjuvant bisphosphonates. Combination chemotherapy has been found to reduce the annual odds of recurrence and death in pre- and postmenopausal women. The benefits, however, are on average less in older patients. Anthracycline-based regimens are more effective than traditional regimens of cyclophosphamide, methotrexate, and fluorouracil (CMF). The benefits of adjuvant cytotoxic and endocrine treatments are additive. There is considerable debate as to the role of taxanes in adjuvant therapy. Improved outcome has been observed in one large trial, especially in those patients with ER-negative tumours. High-dose chemotherapy has not fulfilled its early promise. Ovarian suppression and/or tamoxifen remain the treatments of choice. The annual odds of relapse and death have been reduced by approximately one-third and one-quarter, respectively. Several very large studies are in progress to assess the potential of aromatase inhibitors in the adjuvant setting. Direct comparisons with tamoxifen, as well as switching after several years from tamoxifen to an aromatase inhibitor, are strategies under evaluation. Early results from one of these trials evaluating anastrozole (the Arimidex, Tamoxifen, Alone or in Combination [ATAC] trial) has reported a reduced relapse rate after a median follow-up of 3 years in favour of anastrozole. However, this was at the expense of accelerated bone loss, and strategies to minimise this side effect of aromatase inhibitors are under investigation. Although many studies have indicated that bisphosphonates prevent the development of metastatic bone disease in animals, the clinical role of prophylactic bisphosphonates in early breast cancer is not clearly defined. Three studies with oral clodronate have been published, two of them indicating a protective effect on the development of bone metastases and improved survival, and one suggesting a disadvantage to the use of adjuvant clodronate. Further large adjuvant trials with clodronate and zoledronic acid are in progress. Adjuvant bisphosphonates also have been found to reduce bone loss associated with cancer treatments and preserve skeletal health. It may be possible to replace the current oral regimens for prevention of bone loss with a single annual infusion of the highly potent bisphosphonate zoledronic acid.
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PMID:Current and future status of adjuvant therapy for breast cancer. 1254 90

Endocrine therapy remains important in the adjuvant treatment of pre- and postmenopausal women. Adjuvant ovarian ablation with or without tamoxifen produces effects which are equivalent to those of CMF (cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy in premenopausal women with oestrogen receptor (ER) and/or progesterone receptor (PgR) positive breast cancer. Tamoxifen alone is also effective in these women. Concurrent use of tamoxifen and ovarian ablation may be even more effective, but more studies are needed. Tamoxifen remains a standard adjuvant therapy for postmenopausal women with ER and/or PgR positive tumours. Current information supports the use of 5 years of tamoxifen but additional studies comparing 5 years to longer duration are ongoing. The aromatase inhibitor (AI) anastrozole has now been demonstrated to be better than tamoxifen in preventing recurrence in early reports from the Arimidex vs Tamoxifen And the Combination (ATAC) Trial. Ongoing trials of this and other AIs before, after, concurrent with, or substituted for tamoxifen in the adjuvant setting may soon revolutionize our approach for postmenopausal women. Adjuvant bisphosphonates have been shown to reduce the incidence of bone metastases and improve survival in two of three published adjuvant trials and are being further studied. Her-2 neu status is being explored as a predictive factor for selection of endocrine therapy, but is not yet considered standard for this purpose.
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PMID:The best use of adjuvant endocrine treatments. 1465 27

Tamoxifen is the standard first-line endocrine therapy for breast cancer, but recent data indicate that it is likely to be replaced by the effective aromatase inhibitors (AIs), in both the metastatic and adjuvant settings. Aromatase inhibitors induce complete oestrogen deprivation that leads to clinically significant bone loss. Several ongoing or planned trials combine AIs with bisphosphonates, even more so that recent data reveal that clodronate may reduce the incidence of bone metastases and prolong survival in the adjuvant setting. Bisphosphonates can inhibit breast cancer cell growth in vitro, but they have never been studied in steroid-free medium (SFM), an in vitro environment that mimics the effects of AIs in vivo. Quite surprisingly, in SFM, clodronate stimulated MCF-7 cell growth in a time- and dose-dependent manner by up to two-fold (crystal violet staining assay), whereas it had no mitogenic activity in complete medium. The bisphosphonate similarly increased the proliferation of IBEP-2 cells, which also express a functional oestrogen receptor (ER), while it weakly inhibited the growth of the ER-negative MDA-MB-231 cells. Expectedly, 17beta-oestradiol stimulated the growth of MCF-7 and IBEP-2 cells cultured in SFM, and had no effect on MDA-MB-231 cells. Moreover, partial (4-OH-tamoxifen) and pure antioestrogens (fulvestrant, ICI 182,780), in combination with clodronate, completely suppressed the mitogenic effect of the bisphosphonate, suggesting that it was mediated by an activation of ER. In accordance with this view, clodronate induced ER downregulation, weakly increased progesterone receptor expression, and stimulated the transcription of an oestrogen-responsive reporter gene. In conclusion, we report a previously unknown stimulatory effect of clodronate on MCF-7 cells grown in SFM, in vitro conditions that are potentially relevant to the use of AIs for breast cancer. Moreover, our data suggest that ER is involved in these effects of clodronate on cancer cell growth.
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PMID:Steroid-free medium discloses oestrogenic effects of the bisphosphonate clodronate on breast cancer cells. 1547 66

Tumor cells in bone can induce the activation of osteoclasts, which mediate bone resorption and release of growth factors and calcium from the bone matrix, resulting in a cycle of tumor growth and bone breakdown. Targeting the bone microenvironment by the inhibition of RANKL, an essential mediator of osteoclast function, not only prevents tumor-induced osteolysis but also decreases skeletal tumor burden in preclinical models. The inhibition of skeletal tumor progression after the inhibition of osteoclasts is via interruption of the "vicious cycle" of tumor/bone interactions. The majority of breast cancer patients at risk for bone metastases harbor estrogen receptor-positive (ER+) tumors. We developed a mouse model for ER+ breast cancer bone metastasis and evaluated the effect of RANKL inhibition on tumor-induced osteolysis and skeletal tumor growth both alone and in combination with tamoxifen. Luciferase-labeled MCF-7 cells (MCF-7Luc) formed metastatic foci in the hind limbs following intracardiac injection and caused mixed osteolytic/osteoblastic lesions. RANKL inhibition by OPG-Fc treatment blocked osteoclast activity and prevented tumor-induced osteolysis, as well as caused a marked decrease in skeletal tumor burden. Tamoxifen as a single agent reduced MCF-7Luc tumor growth in the hind limbs. In a combination experiment, OPG-Fc plus tamoxifen resulted in significantly greater tumor growth inhibition than either single agent alone. Histologic analysis revealed a decrease in the proliferation of tumor cells by both single agents, which was enhanced in the combination treatment. Upon treatment with OPG-Fc alone or in combination with tamoxifen, there was a complete absence of osteolytic lesions, demonstrating the ability of RANKL inhibition to prevent skeletal related morbidity in an ER+ model. The combination approach of targeting osteoclasts and the bone microenvironment by RANKL inhibition and the tumor directly via hormonal therapy may provide additional benefit to reducing skeletal tumor progression in ER+ breast cancer patients.
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PMID:RANKL inhibition combined with tamoxifen treatment increases anti-tumor efficacy and prevents tumor-induced bone destruction in an estrogen receptor-positive breast cancer bone metastasis model. 2292 64

Patients with estrogen-receptor-positive advanced breast cancer are treated with endocrine therapy. The majority of breast cancer localizations show 18F-fluorodeoxyglucose (FDG) uptake at positron emission tomography (PET) examination. In these patients, the metabolic flare after therapy is common and was proposed as an index of therapy efficacy. Nevertheless, prolonged persistence of flare can lead to misinterpretation. We describe a case of a patient with invasive ductal breast cancer with bone metastases at bone scintigraphy and FDG PET scan and with expression of estrogen receptors. Initially, the patient underwent endocrine therapy in addition to a biphosfonate. Owing to progression observed in a bone scan, Tamoxifen was substituted with aromatase inhibitors. Successive bone scan examinations showed stabilization with a marked clinical improvement. A second FDG PET was performed 28 months after the first examination and showed a metabolic flare phenomenon with concomitant partial calcification of osteolitic lesions. This is an unusual case of prolonged metabolic flare.
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PMID:Paradoxal metabolic flare detected by 18F-fluorodeoxyglucose positron emission tomography in a patient with metastatic breast cancer treated with aromatase inhibitor and biphosphonate. 2459 81

It is well known that fractures increase the risk of morbidity and mortality. The various mechanisms responsible for bone loss in cancer patients may have a different impact depending on the characteristics of the clinical case and correlates with the therapies used, or caused by the therapies used against cancer. Some hormonal treatments cause hypogonadism, event which contributes to the progressive loss of bone mass. This is detectable in patients with breast cancer receiving determines that estrogen-deprivation and in men with prostate cancer with therapies that determine androgen deprivation. Chemotherapy treatments used in cancer patients have reduced bone mass. In addition, low bone mass is detectable in patients with lymphoma treated with corticosteroids or radiation or alkylating agents. In premenopausal patients suffering from breast cancer, treatment with cytotoxic therapy or ablation of ovarian function, can lead to an 8% reduction in bone mineral density at the spine and 4% in the femur. With a chemotherapy regimen in CMF, the reduction of BMD is 6.5%; this bone loss is not recovered after discontinuation of therapy. Tamoxifen given for five years reduces bone remodeling and cause a 32% increase in the risk of osteoporotic fractures when used in premenopausal. After menopause, tamoxifen has a protective effect on bone mass, with a reduced risk of new fractures. Aromatase inhibitors in post-menopausal women, depending on the formulation can cause different effects on the reduction of BMD and fracture risk. We have in fact steroids, exemestane and nonsteroidal, letrozole and anastrozole. Patients at increased risk of fragility fractures should undergo preventive therapies as soon as possible after tests performed for the study of bone health. They can be used DEXA and the FRAX algorithm, which can define a secondary osteoporosis. Prevention and treatment of the increased risk of osteoporotic fracture is to maintain adequate levels of calcium and vitamin D. Bisphosphonates and denosumab are used for the management of bone remodeling and bone loss induced by cancer treatments. Bisphosphonates also have anti-tumor effects per se, which are expressed in potentially prevent the development of bone metastases. In men with metastatic prostate cancer and which is induced androgen deprivation, it is usefully used denosumab 120 mg monthly or zoledronic acid 4 mg monthly.
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PMID:Prevention and treatment of bone fragility in cancer patient. 2660 36


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