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 glycosylation pattern of brain metastases originating from primary breast carcinomas was investigated using Helix pomatia agglutinin (HPA), a lectin which recognises N-acetyl-galactosamine (GalNac) residues of glycoconjugates. In a previous retrospective study this lectin was shown to label only those primary breast cancers that metastasised. To explore this as a clinical marker of metastatic breast cancer behaviour it is necessary to analyse the HPA binding pattern of metastases to see if this differs from primary cancers. To test the question if brain metastases commitently retain this trait of metastatic primary tumors, we studied Helix pomatia binding pattern of brain metastases removed by surgical excision and immediately fixed and processed. Brain metastases from 16 patients with breast cancer were obtained, 13/16 metastases showed binding to the cytoplasm in the majority of cancer cells, 3/16 did not show binding to cancer cells. Normal adjacent brain showed binding to red blood cells, to capillary endothelium of several biopsies and to rare neurones; this binding did not relate to cancer cell binding. Therefore we conclude that HPA is a relatively stable marker for metastasizing breast cancer cells.
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PMID:Helix pomatia lectin binding pattern of brain metastases originating from breast cancers. 162 91

L-[methyl-11-C]methionine (11C-methionine) uptake of seven primary breast cancers, four soft tissue metastases of breast cancer, and three other breast lesions was studied by positron emission tomography (PET). 11C-methionine accumulation was assessed by calculating the standardised uptake value (SUV). The mean SUV for breast cancer was 8.5 +/- 3.3 (s.d.), while the maximal uptake in the liver was 12.4 +/- 1.6, in the bone marrow 5.8 +/- 0.7, and in the myocardium 3.4 +/- 0.6. All eight malignant tumours larger than 30 mm in diameter accumulated clearly 11C-methionine, whereas none of the three smaller cancers (from 12 to 15 mm in diameter) were visualised. Strong uptake of 11C-methionine was associated with a large S-phase fraction (SPF) measured with flow cytometry (r = 0.77, P = 0.01), and the non-visualised cancers had all a small SPF (less than 5.5%). One benign tumour (an abscess) accumulated slightly 11C-methionine. The results indicate that both primary and metastatic breast cancer can be effectively imaged with 11C-methionine by PET, and that the accumulation of 11C-methionine may correlate with the proliferation rate of breast carcinoma.
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PMID:Uptake of 11C-methionine in breast cancer studied by PET. An association with the size of S-phase fraction. 166 33

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).
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PMID:Phase II trial of taxol, an active drug in the treatment of metastatic breast cancer. 168 8

Complications of breast cancer involving the skeleton include hypercalcaemia, bone pain and fracture. These complications arise because of progressive osteolysis which is in turn dependent on the activation of osteoclasts by tumour and host tissues. Clodronate is a powerful inhibitor of osteoclastic bone resorption which led us to evaluate its potential in metastatic breast cancer. When given intravenously it lowers serum calcium in the majority of hypercalcaemic patients. A convenient regimen is 600 mg iv as a single dose infused over several hours. We have additionally shown in a double-blind cross-over study that this regimen also has a significant effect on bone pain. This had led us to assess the longer term effects of clodronate by mouth in a prospective double-blind study of patients with established skeletal metastases. These studies are not yet complete but the agent appears to prevent hypercalcaemia and trends are emerging which indicate that the incidence of bone pain and fractures may also decrease.
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PMID:Treatment of skeletal disease in breast cancer with clodronate. 172 12

The reported studies of clodronate in the management of osteolytic bone metastases suggest a significant palliative role for this drug. In this paper we report on analysis of the hospital costs associated with the management of osteolytic metastatic disease, and an estimate of the potential cost/benefit impact of clodronate therapy. Two separate patient populations were assessed retrospectively. The first, a sample of 120 patients with symptomatic bone metastases who had died from metastatic breast cancer over the period 1980-1990, was used to define the natural history of the disease. A second non-concurrent patient group of 337 patients was evaluated to determine the mean cost of all hospital admissions for patients with bone metastases from breast carcinoma. The length of stay and costs for hospital admissions related to the bone metastases were also assessed, in addition to the cost of out-patient radiation therapy. Our cost/benefit value analysis suggests that there are significant savings to be gained from the use of clodronate if a 20% or greater reduction occurs in the incidence of fractures, hypercalcaemia, and hospital-based treatment for pain control (via radiotherapy). We also speculate that the quality of life of patients with osteolytic bone metastases may be improved with this agent.
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PMID:An evaluation of the potential cost reductions resulting from the use of clodronate in the treatment of metastatic carcinoma of the breast to bone. 172 13

Lactic acidosis B is a rare metabolic complication of malignancy. It usually is associated with advanced and extensive metastatic disease. The authors report a case in which lactic acidosis was the presenting feature of a previously undiagnosed case of metastatic breast cancer in a pregnant woman and that resolved with successful antineoplastic treatment. The authors review the likely cause and management of the condition.
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PMID:Lactic acidosis. A presentation of metastatic breast cancer arising in pregnancy. 172 74

The development of new and effective marker substances has optimized tumor-marker-guided follow-up programs to monitor generalization of disease and to assess the therapeutic outcome. Isoferritins of placental origin were first determined in the serum of patients with lymphoproliferative disease by way of the recently developed monoclonal antibody CMH-9. We have set up an Austro-Israeli working group and analysed 64 patients in terms of the sensitivity of placental ferritin (PLF) compared with the standard markers carcinoembryonic antigen (CEA) and mucinous-like cancer-associated antigen (MCA) in patients with metastatic breast cancer. We have additionally evaluated the importance of combined marker determination. Analysis of the data in view of site of metastatic spread yielded satisfying results both for PLF (sensitivity 70.4%) as well as MCA (sensitivity 76.9%) for visceral metastases; a combination of these two markers revealed a striking sensitivity of 88.4%, which, however, could not be improved by adding the third marker (CEA). With regard to non-visceral metastases, CEA and MCA were clearly superior.
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PMID:Placental isoferritin (PLF) in comparison with MCA and CEA in advanced breast cancer--first data from a pilot study. 177 47

Twenty-two patients with previously untreated metastatic breast cancer and nineteen patients with refractory metastatic breast cancer were treated with trimetrexate (TMTX). Patients received TMTX 8 mg/m2/day if previously treated or 12 mg/m2/day if previously untreated, both given by intravenous bolus days 1-5, every 21 days. None of the patients previously treated for metastatic disease responded to TMTX. There was one partial responder among the 22 patients with previously untreated metastatic disease. The primary toxicity was hematologic and occurred more frequently in patients with a pleural effusion, low serum protein or albumin, or poor performance status. There were three toxic deaths. The study for previously untreated patients required cyclophosphamide, doxorubicin, and 5-fluorouracil (CAF) after 4 cycles of TMTX. This study design for previously untreated patients allows the Cancer and Leukemia Group B (CALGB) to prospectively evaluate the activity of new agents in "chemotherapy-sensitive" metastatic breast cancer.
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PMID:Trimetrexate in untreated and previously treated patients with metastatic breast cancer: a Cancer and Leukemia Group B study. 182 34

Continuous administration of gonadotrophin-releasing hormone (GnRH-)analogues leads to a receptor-down regulation of pituitary GnRH-receptors and subsequently inhibits ovarian hormone production. Since October, 1984, 118 evaluable pre- and perimenopausal patients (median age 42, range 25-55 years) with metastatic breast cancer were entered into an open phase II multicenter trial to evaluate efficacy of this new treatment modality. Patients were treated with the GnRH-analogue Goserelin (3.6 mg depot s.c. every 4 weeks) as first line therapy and followed up until progression. Mean serum gonadotrophins LH and FSH were significantly suppressed by Goserelin. Within 2-3 weeks, mean serum E2 values decreased to values seen in castrated women (less than 30 pg/ml). Overall objective response with complete and partial remissions (CR + PR) was achieved in 44.9% of patients with a median time to progression (mTTP) of 59 weeks, (range 20-163 weeks), no change (NC) in 28.0% with a mTPP of 27 weeks (range 16-101 weeks), and progression (P) in 27.1%. Responses were seen in ER-positive as well as ER-negative tumors, and in patients with different sites of metastases (locoregional, bone, visceral, multiple). The value of different prognostic factors in relation to response rates, time to progression and time to death (overall survival) is discussed. Median overall survival (time from beginning of palliative Goserelin treatment to death) was 148 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The depot GnRH analogue goserelin in the treatment of premenopausal patients with metastatic breast cancer--a 5-year experience and further endocrine therapies. Cooperative German Zoladex Study Group. 182 49

Four hundred fifteen patients with metastatic breast cancer with known hormone receptor status received primary treatment with tamoxifen. Measured values for the estrogen receptor (ER, i.e., with estrogen binding) followed a continuous distribution (range, 3 to 1000 fmol/mg of protein). These values correlated positively with age. The response to treatment with tamoxifen correlated with the ER level, with response rates of approximately 80% when the ER level was greater than 30.1 fmol/mg of protein. Two hundred eighteen (218 of 415, 52%) patients had progesterone receptor (PR) values greater than 10 fmol/mg. The PR positivity correlated with the ER level. Patients with PR levels greater than 10 fmol/mg of protein (124 of 226, 55%) had a significantly higher response rate than those with values less than 10 fmol/mg of protein (45 of 189, 24%). However, in a multivariate analysis including both receptor levels, age, site, and number of metastases, only the ER level was significant in predicting the response to treatment with tamoxifen. A quantitative estimation of the ER level thus is the best predictor of response to hormonal treatment with tamoxifen for advanced breast cancer.
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PMID:The value of estrogen and progesterone receptor determinations in advanced breast cancer. Estrogen receptor level but not progesterone receptor level correlates with response to tamoxifen. 185 86


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