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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine therapies for breast cancer have been used for more than a century. The concept that changing the hormonal balance of the patient with breast cancer could lead to changes in tumor growth and regression of metastatic disease was recognized even before hormones and endocrine agents were available. Ablation of ovaries, adrenals, or hypophysis was used in advanced disease to obtain tumor regression and control of symptoms. Ovarian ablation was also tested for operable breast cancer showing a significant beneficial treatment effect. Several endocrine agents have been developed in recent years: estrogens, androgens, progestins, antiestrogens, aromatase inhibitors, gonadotropin-releasing hormone analogs, antiprogestins, and antiandrogens. The use of some of these agents in advanced disease led to investigations in early breast cancer: tamoxifen was the drug which was most extensively tested, showing a significant long-term benefit for treated patients. Progestins (medroxyprogesterone acetate) and aromatase inhibitors (aminoglutethimide) were also tested in a few clinical trials, but no conclusive recommendations for their use in patients with operable disease may be formulated. The most important current challenges for the appropriate use of endocrine therapies in breast cancer include (1) understanding the effect of endocrine therapies and the mechanisms of resistance associated with their use; (2) developing new agents with novel endocrine antitumor effect; (3) defining the best way to combine endocrine agents with cytotoxics or with other endocrine manipulations; and (4) identifying long-term effects of endocrine agents in terms of disease control and prevention, as well as desirable and undesirable side effects.
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PMID:Endocrine therapies of breast cancer. 875 75

Hormonal agents play a critical role in the palliation of advanced breast cancer, as well as adjuvant therapy to surgery and radiation in patients with primary breast cancer. Tamoxifen appears to be the therapy of choice for the initial treatment of metastatic breast cancer in both premenopausal and postmenopausal women, although some clinicians prefer oophorectomy or the use of luteinizing hormone releasing hormone analogues in premenopausal patients. Historically, second-line hormonal therapy for metastatic disease has been with a progestin; however, due to the troubling side effects of weight gain and dyspnea, progestins may soon be replaced by aromatase inhibitors. The development of new antiestrogens lacking estrogen-agonist activity for metastatic disease is in its earliest clinical developmental phases. For adjuvant therapy in postmenopausal women, there is conflicting evidence as to whether the combination of a hormonal agent (ie, tamoxifen) plus chemotherapy provides an advantage over hormonal therapy alone. In premenopausal women areas of active investigation include combination hormonal therapy (eg, tamoxifen plus luteinizing hormone releasing hormone analogues or oophorectomy) and combination chemohormonal therapy (concomitant v sequential). Tamoxifen had been associated with rare cases of thromboembolic events and secondary endometrial cancers. The etiology of these secondary cancers is unclear and controversial; however, the benefits of tamoxifen far outweigh the risks for both palliative and surgical adjuvant therapy. The success of tamoxifen in preventing cancer recurrence in the contralateral breast has led to clinical investigation of the drug for the chemoprevention of breast cancer in women at high risk for development of the disease. The role of tamoxifen for this indication remains to be determined following completion of the National Surgical Adjuvant Breast and Bowel Project trial in North America and additional trials in the United Kingdom and Italy.
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PMID:Hormonal approaches to breast cancer treatment and prevention: an overview. 882 59

Formestane (4-hydroxyandrostenedione) is an aromatase inhibitor which significantly reduces plasma levels of estrogen and has shown antitumour activity in postmenopausal women with breast cancer. Objective response rates in heavily pretreated patients with advanced breast cancer generally range between 20 and 30% during treatment with intramuscular formestone 250 or 500mg once every 2 weeks, and a further 20 to 30% of patients experience disease stabilisation. The median duration of response is between 8 and 14 months. Highest response rates are observed in soft tissue metastases, in patients with estrogen-responsive tumours and in those showing a response to previous endocrine therapy. Furthermore, there is some evidence to suggest that higher response rates are achieved with formestane 500 versus 250mg once every 2 weeks. In comparative studies, the clinical efficacy of intramuscular formestane 250mg did not differ significantly from that of oral megestrol when administered as second-line endocrine therapy to patients with advanced disease in whom previous tamoxifen therapy had failed. In addition, formestane produced a response rate, duration of response and overall survival rate that was not significantly different from that of oral tamoxifen when administered as first-line endocrine therapy to patients with advanced disease, but tamoxifen was superior in some measures. Further investigation of these 2 agents, including the higher dosage of formestane (500mg), is necessary to confirm their relative efficacies. Formestane is well tolerated by the majority of patients; adverse events rarely necessitate cessation of therapy. The most common adverse events are local reactions at the injection site and systemic events usually related to the effect of the drug on the hormonal milieu. The systemic tolerability of formestane is similar to that of tamoxifen but better than that of megestrol. Thus, formestane is effective and well tolerated as first-line endocrine therapy for advanced disease. However, at present, it is unlikely to challenge tamoxifen in this indication, based on recent findings from a large comparative study and the fact that formestane requires intramuscular administration. Nonetheless, formestane, which appears to have a better tolerability profile than other currently available second-line agents (including megestrol and the aromatase inhibitor aminoglutethimide), is a valuable drug for the second-line treatment of postmenopausal women with advanced breast cancer.
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PMID:Formestane. A review of its pharmacological properties and clinical efficacy in the treatment of postmenopausal breast cancer. 889 26

We report a 15-year-old boy with hepatocellular carcinoma (HCC) of the fibrolamellar type. He presented with advanced disease and a non-resectable tumor. Clinical features included marked gynecomastia which had been present for 3 years, failure to enter puberty, and failure to thrive. These features might have been due to a high aromatase activity of the tumor. The course of the illness suggested that the tumor had been present for at least 3 years prior to diagnosis. At diagnosis the patient had multiple metastases which included infiltrated ascites. Cytogenetic analysis of the ascites revealed a near triploid karyotype with cell-to-cell variation and an abnormality of chromosome 1 q. This to our knowledge is the first karyotype report of fibrolamellar HCC in a child.
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PMID:A childhood fibrolamellar hepatocellular carcinoma with increased aromatase activity and a near triploid karyotype. 898 50

Tamoxifen (TAM) is widely used as therapy in early breast cancer and first-line endocrine therapy in metastatic disease. Despite this therapy, many patients relapse and an important question is: What is the preferred sequence of endocrine therapies in metastatic breast cancer (MBC). While treatment with oophorectomy, aminoglutethimide or progestins have been a logical choice after failure to Tamoxifen recent research has extended the options for endocrine therapy of MBC. New selective aromatase inhibitors (AI) are now in clinical use. The first commercially available of these inhibitors is LENTARON. The active ingredient of LENTARON is a steroidal compound 4-OH-androstenedione: Formestane. It is presented as a depot formulation and applied as an i.m. injection of 250 mg every second week. Previous findings from phase II trials have indicated similar activity as other endocrine treatment modalities. Clinical investigations in properly conducted phase III trials have revealed that the efficacy of LENTARON matches the results which can be obtained with TAM and Megace in trials of first and second-line endocrine therapy. Fifty-four and 51% of MBC patients, respectively, did benefit from therapy with LENTARON in these phase III trials by achieving objective responses or stable disease. Moreover, similar overall survival was seen. The systemic tolerability of LENTARON is comparable to that of TAM, and LENTARON seems less systemically toxic than Megace. Local side effects occured in approximately 7% of the patients giving rise mainly to pain or inflammation at the injection site. In elderly patients, LENTARON therapy assures compliance and no interference with other oral medications has been observed. In conclusion, since the endocrine treatment modalities are comparable in terms of efficacy the optimal sequence of these treatments is based upon differences in tolerability. Patients previously treated with Tamoxifen and with a high probability of a further endocrine response could preferably be treated with a selective AI like LENTARON as second-line endocrine therapy followed by a progestin upon progression in responders.
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PMID:Proper sequence of endocrine therapies in advanced breast cancer. 914 64

Bone metabolism marker evaluation is expected to play an auxiliary role in the diagnosis and follow-up of bone metastases in patients affected by different types of neoplasms. In this study we have evaluated osteoblastic and osteoclastic markers in 18 patients with bone metastases from breast cancer at diagnosis and for 1 year of follow-up during treatment with the aromatase inhibitor formestane. Osteoblastic markers include the carboxy-terminal propeptide of type I procollagen, the bone-specific alkaline phosphatase and the bone GLA protein. The carboxy-terminal cross-linked telopeptide of type I collagen (ICTP) was evaluated as a marker of osteoclastic activity. The patients were classified into three groups according to clinical response. A good correlation between marker level modifications and clinical evolution of skeletal metastases was observed for all the examined markers. Patients with progressive disease showed increasing levels of all markers, whereas patients in regression showed a reduction compared to the basal levels; patients with stable disease fell in between these two categories. We also found that basal ICTP values have prognostic significance: in the stable and progressive disease group they were higher than in the partial response group.
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PMID:Serum markers of bone metastases in postmenopausal breast cancer patients treated with formestane. 921 4

The introduction of new drugs may offer significant hope for improvement in the treatment of breast cancer. They include new cytotoxic agents such as Taxanes, Topoisomerase inhibitor, MDR modulator, new hormone such as 3rd generation nonsteroidal aromatase inhibitor, pure antiestrogen for patients with refractory metastatic breast cancer and new bisphosphonates for those who have metastases to bone. Therefore, some reports evaluating such new drugs were reviewed. Japanese studies revealed response rate of Taxanes in the treatment of metastatic breast cancer as follows; Six out of 22 (27%) with 1 CR for 24 hours infusion, 21 out of 52 (34%) with 2 CR for 3 hours infusion of paclitaxel respectively, 21 out of 31 (41%) with 2 CR for 1 hour infusion, and 32 out of 72 (44%) with 5 CR for 1 hour infusion of Docetaxel, In addition, the MTD of the combination was reached at dose level with 60 mg/sqm of Docetaxel and 400 mg/sqm of cyclophosphamide. As regards hormone therapy, thirty four out of 176 (19%) with 5 CR were observed in phase II study of Fadrozol but results from the phase II study of 3rd generation aromatase inhibitor is not yet accomplished in Japan. However, any european reports did not show a difference in response rate in patients with tamoxifen refractory breast cancer between newer aromatase inhibitor and megasterol, and a good choice of hormones in the treatment of metastatic breast cancer appears to be difficult.
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PMID:[New drugs in metastatic breast cancer--1997]. 935 Feb 35

A significant percentage (50-70%) of patients with metastatic breast carcinoma (MBC) will have disease involving the bony skeleton. Clonal selection mediated by parathyroid hormone-related protein and other factors may explain the high incidence of osseous metastases in MBC. The presence of specific growth factors and cytokines in the microenvironment of bone may contribute to the successful establishment and growth of metastatic lesions and also might determine response or resistance of these lesions to chemotherapy or hormonal therapy. Osteolytic bone lesions in MBC frequently give rise to serious clinical problems including bone pain, pathologic fracture, hypercalcemia, and neurologic complications. MBC often is treated with systemic chemotherapy or hormonal therapy. The purpose of this article was to review the recent published literature describing the impact of systemic chemotherapy and hormonal therapy of MBC on the response of bone lesions and their clinical course and complications. Evaluating the response of bone lesions can be problematic and may be complicated by the phenomenon of "tumor flare" that may be observed with either chemotherapy or hormonal therapy. Use of the International Union Against Cancer criteria for the response of bone lesions is recommended. Several studies report objective responses (20-60%) of lytic bone metastases to standard combination chemotherapy regimens such as cyclophosphamide, methotrexate, and 5-fluorouracil and cyclophosphamide, doxorubicin, and 5-fluorouracil, mitoxantrone and 5-FU, newer combinations, and single agents including paclitaxel and docitaxel but responses to vinorelbine may be less frequent. Complete responses of bone lesions to chemotherapy are rare but partial responses and disease stabilization can lead to long term patient benefit. A series from the M. D. Anderson Cancer Center of patients with bone metastases treated with 5-FU, doxorubicin, and cyclophosphamide chemotherapy reported a median duration of response of 14 months. In a recent multicenter study of 195 patients with lytic lesions from MBC treated with chemotherapy, the objective response rate (complete response + partial response) in bone was 18% and 65% of the patients developed at least 1 morbid skeletal event with a median onset of 7.0 months from the start of chemotherapy. Hormone-dependent breast carcinoma has a proclivity to metastasize to bone. In earlier studies comparing aminoglutethimide or medroxyprogesterone acetate with tamoxifen, a higher response rate of bone metastases was observed for the first two agents. However, in more recent studies comparing newer aromatase inhibitors, such as anastrozole, fadrozole, and letrozole, with megestrol acetate, there were no significant differences in rates of response in bone. Patients with MBC with bony lesions respond to both chemotherapy and hormonal therapy and can have a prolonged survival. Therefore such patients are in a more favorable position to benefit from adjunctive supportive therapy such as bisphosphonates intended to reduce skeletal morbidity.
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PMID:Issues concerning the role of chemotherapy and hormonal therapy of bone metastases from breast carcinoma. 936 31

The choice of endocrine agent for breast cancer depends on the menopausal status of the patient, the stage of disease, prognostic factors, and the toxicity profile of the agent. Endocrine therapies are typically given sequentially, with the least toxic therapy given first. Tamoxifen is considered first-line endocrine therapy for all stages of breast cancer. New antiestrogens in development include nonsteroidal agents related to tamoxifen and pure steroidal antiestrogens. Luteinizing hormone-releasing hormone agonists are an effective form of endocrine therapy for premenopausal women with advanced breast cancer, and aromatase inhibitors are effective in postmenopausal women. Newer and more selective aromatase inhibitors that are p.o. active and have improved side-effect profiles have been developed. Recent trials have found these agents to improve survival in comparison to the progestins; thus, aromatase inhibitors are replacing progestins as second-line therapy for metastatic disease. Current trials are examining the potential role of aromatase inhibitors as first-line therapy for metastatic disease or as adjuvant therapy for early disease. The antiprogestins and antiandrogens studied thus far have had only limited success in breast cancer clinical trials.
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PMID:Update on endocrine therapy for breast cancer. 953 18

Aromatase inhibition is now an acknowledged second line treatment modality for advanced breast cancer in postmenopausal women. Aminoglutethimide is an inhibitor of adrenal steroid biosynthesis and blocks the conversion of cholesterol to pregnenolone, and therefore reduces levels of adrenal androgens, which are a source of estrogens in both premenopausal and postmenopausal women. Aminoglutethimide has produced antitumor response rates of 35% in unselected patients, most of whom have undergone prior therapy with either chemotherapy or hormonal manipulation. As is true of other hormonal responses, high response rates of up to 70% are observed in patients who are ER and/or PR positive. The reason why these drugs are currently used after tamoxifen is mainly due to the side effects of aminoglutethimide, which impairs the mineralocorticoid and glucocorticoid synthesis. New, less toxic compounds appear, which block the conversion of androstenedione to estrone and efficiently suppress plasma estrogen levels., e.g. formestane, anastrozole and letrozole. Aromatase inhibitors are now being compared to tamoxifen as first-line endocrine treatment in relapsing patients. If these trials confirm a similar or better response rate to new aromatase inhibitors compared to tamoxifen, the time will come to study them as the first line adjuvant treatment in non-metastatic disease.
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PMID:[Aromatase inhibitors--new possibilities in treatment of breast carcinoma]. 962 25


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