Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The brain, cranial nerves, leptomeninges, spinal cord, and eye compose the central nervous system (CNS) and are at risk for the development of metastases from breast cancer. Such metastases are diagnosed on the basis of clinical suspicion and substantiated by neuroimaging, resection when indicated, and sampling of cerebrospinal fluid when leptomeningeal metastasis (LM) is suspected. Treatment is aimed at palliation of symptoms and preservation of neurologic function. Historically, conventional radiation therapy has been the mainstay of palliative treatment for brain, cranial nerve, spinal cord, and ocular metastases. However, additional treatment options for brain metastases have been brought about by technological advances in surgery to resect brain metastases, and stereotactic radiosurgery (SRS) to focally irradiate metastases, both of which have been substantiated by data from randomized trials. Ongoing research is aimed at refining criteria to select which patients with brain metastases should undergo surgery and SRS and how these focal therapies should be optimally integrated with whole-brain radiotherapy. Therapy for LM must carefully balance the potential risks and perceived benefits associated with CNS-directed therapies. Despite advances in neuroimaging, surgery, and radiation therapy, novel treatments are needed to improve the effectiveness of treatments for CNS metastases, especially LM, while reducing attendant neurotoxicity.
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PMID:Diagnosis and management of central nervous system metastases from breast cancer. 1453 Apr 93

Central nervous system (CNS) metastases from breast cancer are common and can present as the first or solitary site of disease progression. The CNS has been reported to act as a sanctuary site that denies access to many chemotherapeutic agents. We present here, a series of 10 metastatic breast cancer patients who developed CNS metastases after an initial response to trastuzumab treatment. Forty one patients with metastatic HER2-overexpressing breast cancer, without evidence of CNS involvement prior to the initiation of trastuzumab treatment, were followed during trastuzumab treatment. A neurological evaluation was performed in those patients who developed neurological signs or symptoms during the course of treatment. The clinical course and pattern of CNS involvement in these patients are discussed. Thirty two patients (78%) showed an initial response to trastuzumab treatment. Ten (31%) of the responding patients developed either isolated CNS relapse or concurrent CNS and systemic progression at a median of 43 weeks after the initiation of trastuzumab treatment. Trastuzumab as a single agent was continued following control of brain symptoms in three patients, two showed signs of systemic disease progression at 11 and 15 weeks following the diagnosis of CNS metastases, respectively. In two other patients, trastuzumab in combination with weekly chemotherapy was continued for more than 20 weeks after CNS relapse without evidence of disease progression. The incidence of CNS involvement in our group of patients was higher than expected. With more successful and prolonged systemic anti-tumour effects achieved by novel drug combinations, the risk of developing CNS metastases might be even greater. Evaluation of prophylactic cranial irradiation strategies might be studied for high-risk patients.
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PMID:Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment. 1474 56

As systemic therapy of metastatic breast cancer improves, CNS involvement is becoming a more widespread problem. This article summarizes the current knowledge regarding the incidence, clinical presentation, diagnosis, prognosis, and treatment of CNS metastases in patients with breast cancer. When available, studies specific to breast cancer are presented; in studies in which many solid tumors were evaluated together, the proportion of patients with breast cancer is noted. On the basis of data from randomized trials and retrospective series, neurosurgery and stereotactic radiosurgery (SRS) may prolong survival in patients with single brain metastases. The treatment of multiple metastases remains controversial, as does the routine use of whole-brain radiotherapy (WBRT) after either surgery or SRS. Although it is widely assumed that chemotherapy is of limited benefit, data from case series and case reports suggest otherwise. WBRT, neurosurgery, SRS, and medical therapy each have a role in the treatment of CNS metastases; however, neurologic symptoms frequently are not fully reversible, even with appropriate therapy. Studies specifically targeted toward this group of patients are needed.
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PMID:CNS metastases in breast cancer. 1533 11

About 40% of patients with advanced cancer develop metastases in the central nervous system (CNS), mainly from primary tumors of lung, breast and melanoma. In most of cases there are multiple CNS metastases, making surgery or localized radiosurgery not feasible. The current standard of care for these patients is radiation therapy, which can improve neurologic symptoms but does not have any impact on the patient's overall survival. Temozolomide, capecitabine and gefitinib are safe and active in the treatment of CNS metastases from melanoma/recurrent gliomas, breast carcinoma and lung cancer, respectively. New, orally administered drugs hold a great potential for patients with CNS metastases.
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PMID:Innovative therapy for patients with brain metastases: oral treatments. 1567 90

Amplification or over-expression of the HER2/neu receptor is present in 20-30% of invasive breast cancers and in 60% of intraductal breast carcinomas. Patients with HER2/neu gene aberrations have more aggressive disease, frequent disease recurrence and a shorter survival. Trastuzumab (herceptin) is a monoclonal antibody selectively directed against the HER2/neu receptor. The addition of trastuzumab to chemotherapy in HER2/neu-positive advanced breast cancer patients has increased complete and partial response rates, and prolonged time to progression and overall survival. However, a relatively common failure site in patients administered trastuzumab is the central nervous system (CNS). CNS metastases in these patients seem to develop despite responses achieved in extracerebral sites. This pattern of failure has mainly been attributed to the lack of trastuzumab penetration to the CNS owing to the high molecular weight (145 kDa) of this molecule. Additionally, increased risk of CNS relapse may be associated with improved systemic control of extracerebral metastases and prolonged survival without brain protection (a sanctuary site). Finally, it was postulated that HER2/neu over-expression and/or amplification might predispose to brain metastases. The aim of this article is to discuss the pathophysiology of this phenomenon and its clinical implications.
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PMID:Central nervous system metastases in breast cancer patients administered trastuzumab. 1597 4

The aims were to determine the median survival and prognostic factors of patients with central nervous system (CNS) metastases managed with whole-brain radiation therapy (WBRT), and to explore selection criteria in recently published clinical trials using aggressive interventions in CNS metastases. A retrospective audit was performed on patients managed with WBRT for CNS metastases. Potential prognostic factors were recorded and analysed for their association with survival duration. The proportion of patients with these factors was also compared with those of patients managed under three recently reported studies investigating aggressive interventions, such as radiosurgery and chemotherapy for CNS metastases. Seventy-three patients were treated with WBRT for cerebral metastases over a 12-month period. The median survival of the population was 3.4 months (95% confidence interval: 2.7-4.1), with 6- and 12-month survival rates of 30 and 18%, respectively. Significant prognostic factors for prolonged median survival were Eastern Cooperative Oncology Group status 0-2 (P = 0.015), Medical Research Council neurological functional status 0-1 (P = 0.006), and Recursive Partitioning Analysis Class 2 versus Class 3 (P = 0.020). On multivariate analysis, younger patient age (P = 0.02) and better performance status (P < 0.01) were associated with improved outcome. When comparing these characteristics with selected published studies, our study cohort demonstrated a higher proportion of patients with poor performance status, a greater number of metastases per patient and a higher incidence of extracranial disease. This reflects the selected nature of patients in these published studies. Central nervous system metastases confer a poor prognosis and, for the majority of patients, aggressive interventions are unlikely to improve survival. The use of potentially toxic and expensive treatments should be reserved for those few in whom these studies have shown a potential benefit.
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PMID:Interpreting the improved outcome of patients with central nervous system metastases managed in clinical trials compared with standard hospital practice. 1617 77

Gefitinib is the first inhibitor of the epidermal growth factor receptor that has shown activity in non-small-cell lung cancer (NSCLC), but its potential value in the treatment of central nervous system (CNS) metastases has been rarely assessed. We report 2 cases of patients with CNS metastases responding to gefitinib and a review of all the cases previously published in the literature. Computerized and manual searches were performed to identify reports of patients with NSCLC with CNS metastases treated with gefitinib. Ten reports including 16 cases were identified. Of 18 patients, which included our 2 cases, 14 (78%) were female and 4 (22%) were male. Histologic type was reported in 15 cases, and 12 of them (80%) were adenocarcinomas. Five patients exhibited a complete response (28%) and the rest were partial responses. In addition, we identified 5 series of NSCLC patients with CNS metastases treated with gefitinib, and response rates ranged from 0 to 33%. In conclusion, gefitinib can induce long-lasting responses in NSCLC patients with CNS metastases. Responses have been most frequently observed in female patients with adenocarcinoma. Gefitinib may be an effective and well-tolerated option for selected NSCLC patients with CNS metastases.
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PMID:Activity of gefitinib in central nervous system metastases in patients with non-small-cell lung cancer: two case reports and a review of the literature. 1617 2

Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding.
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PMID:Breast cancer metastasis to the central nervous system. 1619 26

The management of metastatic melanoma in 2005 remains a major clinical challenge. Multidisciplinary treatment planning and careful attention to sites of metastases, tumor biology, and comorbid conditions are critical to making the best clinical decisions for individual patients. No standard of care exists because no systemic therapies have yet shown efficacy in phase III trials. Single-agent or combination chemotherapy has not impacted over-all survival, and response rates are of short duration. High-dose IL-2 produces durable responses in a small subset (7%) of highly selected patients and has considerable toxicity and quality-of-life trade-offs. Biochemotherapy results in overall higher responses, but its impact on overall survival has been disappointing and its toxicity and expense are considerable. Re-searchers are further investigating biochemotherapy modifications with maintenance biotherapy and CNS consolidation in effort to increase durability of responses and prevent or delay the devastating sequela of CNS metastases. Despite a disappointing past, the advancement of science and a better understanding of critical cellular targets and pathways make the future of melanoma research encouraging. Clinical trials are actively studying novel immune potentiators, cytotoxics, and targeted therapies. Combinations of these new agents will likely be necessary to advance the treatment of the dis-ease. All patients should be encouraged to participate in clinical trials.
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PMID:Management of metastatic melanoma 2005. 1663 24

Brain and leptomeningeal metastases from breast cancer carry a poor prognosis and are often less responsive to systemic therapy. It is often thought that systemic therapy has a minimal role in the management of central nervous system (CNS) metastases because of the impermeability of the blood-brain barrier. However, treatments directed to the CNS such as radiation or intrathecal chemotherapy are not effective in managing concurrent non-CNS metastases. We report the long-term control of a woman receiving capecitabine with brain and leptomeningeal metastases. After 3.7 years of capecitabine therapy after whole-brain radiation, the patient remains without neurologic symptoms or deficits, has no evidence of disease on neuroimaging studies, but has a persistent positive cytology. This case report demonstrates that, in principle, systemic therapy can provide long-term complete responses for some patients with CNS metastases. The significance of persistent circulating tumor cells in the CNS in patients without evidence of disease is unclear but should be investigated further.
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PMID:Long-term clinical response in leptomeningeal metastases from breast cancer treated with capecitabine monotherapy: a case report. 1680 Sep 78


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