Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Plasma carcinoembryonic antigen (CEA) and serum enzyme levels of phosphohexose isomerase (PHI), gamma-glutamyl transpeptidase (psi-GTP), and lactate dehydrogenase (LDH) were measured in 147 patients with malignancy. Levels were higher in patients (particularly with G.I., breast and lung cancers) than in normals or in patients with cancer in clinical remission. Elevations of CEA and of all three enzymes in blood were most frequent in patients with hepatic metastases. CEA elevations correlated directly with PHI levels. Seventy-eight percent of patients with metastatic G.I. cancer could be identified by CEA (greater than 5 ng/ml) alone, as well as 38% with breast cancer and 85% with lung cancer; but only 17% of other cancers could be identified by CEA alone. CEA or one or more enzymes was elevated in 64% of metastatic breast cancer patients, 92% of lung cancer and 41% of other cancers, but enzyme measurement did not increase identification of G.I. cancer over that achieved by CEA alone. These findings suggest that circulating levels of CEA, PHI, psi-GTP and LDH may reflect a direct contribution from the malignant tissue and/or liver malfunction secondary to liver replacement.
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PMID:Carcinoembryonic antigen and phosphohexose isomerase, gammaglutamyl transpeptidase and lactate dehydorgenase levels in patients with and without liver metastases. 0 19

A retrospective analysis was undertaken to assess the prognostic role of histologic findings in response to chemotherapy and survival in patients with metastatic breast cancer. Histologic material was available for 395 of 1587 patients treated for metastatic breast cancer at the M.D. Anderson Cancer Center between 1973 and 1984. Chemotherapy consisted of 5-fluorouracil, doxorubicin, and cyclophosphamide or similar drugs, with or without tamoxifen. Maintenance cyclophosphamide, methotrexate, and 5-fluorouracil was continued for 2 years after a cumulative doxorubicin dose of 450 mg/m2 was administered. The histologic distribution was as follows: infiltrating ductal carcinoma, 353; invasive lobular, 14; mixed histology, ten; mucinous, seven; signet ring, four; tubular, three; papillary, two; sarcomatoid, one; and apocrine, one. Because individual histologic types occurred infrequently, the patients were divided into infiltrating ductal and nonductal groups. Baseline patient characteristics included age, performance status, estrogen-receptor status, prior hormone response, disease extent, and levels of alkaline phosphatase, bilirubin, and lactate dehydrogenase. These were similar in the two groups. Significantly more patients with nonductal histology had greater than three metastatic sites. There were also more patients with hemoglobin less than 10 mg/dl and albumin less than 3.5 mg/dl in the nonductal group of patients. However, statistically these factors did not have an impact on the results. There was a 63% response rate (17% complete and 46% partial) for the ductal group and a 60% response rate (12% complete and 48% partial) for the nonductal group. The time from initiation of chemotherapy to disease progression was identical (12 months) for the two groups. Survival from initiation of chemotherapy was not significantly different (22 months for ductal and 27 months for nonductal). Based on this study, the authors conclude that histologic findings have no bearing on patient response to chemotherapy or survival in metastatic breast cancer.
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PMID:Lack of correlation between histologic findings and response to chemotherapy in metastatic breast cancer. 164 36

In this case report the clinical course of a female patient with metastatic breast cancer receiving a mild cytostatic regimen with chlorambucil, methotrexate and prednisone is described. She developed an unusual clinico-pathological syndrome with pancytopenia, fever and bone pain resulting from a bone marrow necrosis. The clinical course illustrates the great diagnostic difficulties and the potential benefit from rapid identification of this prognostically very poor event. Leading symptoms such as fever, bone pain, pancytopenia, an increase in the sedimentation rate, in lactate dehydrogenase and alkaline phosphatase in serum are often misinterpretated as tumor progression with bone or hepatic metastases and bone marrow carcinomatosis. An iliac crest aspirate and biopsy detects the diagnosis of a marrow necrosis. These symptoms should be kept in mind in order to avoid a diagnostic pitfall resulting from a misinterpretation of the morphological picture as necrotic metastasis in bone marrow or as an artefact. It is assumed that, in addition to the underlying malignant disease, cytostatic therapy with chlorambucil, methotrexate and prednisone triggers this event.
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PMID:[Bone marrow necrosis in a patient with metastatic breast cancer in chemotherapy with chlorambucil, methotrexate and prednisone]. 254 86

We determined the effect of long-term freezer storage and repeated thawing and freezing of serum on concentrations of electrolytes (sodium, potassium, calcium, and phosphate), enzymes (aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, and creatine kinase), total protein, tumor markers (carcinoembryonic antigen and alpha-fetoprotein), and other substances. Vials (1 ml) of frozen serum from a single blood drawing from 40 women with no breast disease and 70 with benign breast disease were analyzed annually from 1983 to 1987. Blood had been obtained from 40 subjects in 1978, 40 in 1980, and 30 in 1983. Thawing and refreezing studies were done in two ways: (1) serum samples from 30 subjects with benign breast disease were thawed at weekly intervals for 6 weeks and (2) serum samples from 30 patients with stage IV breast cancer were analyzed for alpha-fetoprotein and carcinoembryonic antigen, and serum specimens from 23 patients with benign breast disease and 7 control subjects were analyzed for lactate dehydrogenase and creatine kinase after thawing and keeping the samples at room temperature for up to 4 hours and then refreezing them. For measuring laboratory variability, duplicate samples were processed. Long-term storage (up to 10 years) and repeated thawing and refreezing did not affect the results of any tested constituents of serum. Although most measurements showed statistically significant variability over test cycles, these differences were thought to be due to laboratory variability.
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PMID:Effect of long-term freezer storage, thawing, and refreezing on selected constituents of serum. 259 13

Since response to chemotherapy is a major determinant of survival in metastatic breast cancer, the purpose of our study was to analyse the predictive factors of response. 1426 patients enrolled into eight consecutive randomised trials of anthracycline-based first-line chemotherapy in metastatic breast cancer, between 1977 and 1992, were analysed. A forward stepwise logistic regression analysis was used. The objective response rate (ORR) to chemotherapy in the total population was 63.6% (95% confidence interval (CI): 61.5-67.7). The complete response rate was 17.5%. Multivariate analysis defined adjuvant chemotherapy, lactate dehydrogenase (LDH), Karnofsky index (KI), and pleural and lung metastases to be the five main variables correlated with ORR. A predictive score was calculated using the coefficient of these five variables, The score was established as follows: -1.32+0.54 (if prior adjuvant chemotherapy) +0.80 (low KI) +0.75 (raised LDH) +0.49 (lung metastases) +0.51 (pleural metastases). A low score (less than -0.78) was associated with an ORR greater than 70.0%, representing 41.2% of our population. An intermediate score (between -0.78 and 0) was associated with an ORR of 50 to 70%, representing 37.5% of our population and a positive score was associated with an ORR of less than 50%, representing 21.3% of our population. This score can be used to predict objective response rates to first-line anthracycline-based chemotherapy. This method now needs to be evaluated prospectively in phase II trials. Identification of various risk groups may also be useful for interpretation and design of clinical trials.
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PMID:Predictive factors of response to first-line chemotherapy in 1426 women with metastatic breast cancer. 1109 3

Of 672 patients with metastatic breast cancer, 24 evaluable patients with primary liver metastases were analysed with regard to their prognostic variables and survival. In 50% of these patients, liver metastases were found within the first 8.5 months after the diagnosis of breast cancer. The median survival of 10 months (range 0-60+ months) was extremely unfavourable. The median survival of hormone-receptor-positive patients (11 months) was significantly longer than that of patients with hormone-receptor-negative tumours (4 months) (P = 0.025). Patients with elevated lactate dehydrogenase (LDH), glutamic-oxaloacetic transaminase (GOT) (> 50 U/I), or bilirubin levels at diagnosis had a significantly shorter median survival than patients with normal laboratory parameters (P = 0.001, P = 0.047, and P = 0.056, respectively). This retrospective study confirms the short survival time for breast cancer patients with liver metastases as initial site of relapse. Hormone-receptor status and the laboratory parameters LDH, GOT, and bilirubin were identified as important prognostic factors for survival.
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PMID:Prognostic significance of liver metastases as first site of generalisation in patients with breast cancer--a retrospective analysis. 1177 75

A 47-year-old woman with metastatic breast cancer developed acute pancreatitis while receiving capecitabine. She had been receiving capecitabine 2000 mg/m2/day; however, when the dosage was increased to 2500 mg/m2/day (the maximum dosage approved by the Food and Drug Administration) she experienced abdominal pain and cramping. These symptoms were followed by nausea and vomiting, palmar-plantar erythrodysesthesia (hand-foot syndrome), and mucositis, resulting in admission to the hospital. Laboratory tests for liver function showed elevated levels of alkaline phosphatase and lactate dehydrogenase. The patient's lipase and amylase levels were also elevated, but an abdominal ultrasound was normal. After bowel rest and intravenous hydration, the patient's liver function tests and lipase and amylase levels returned to normal. Many chemotherapeutic agents have been documented to cause pancreatitis; however, we found no previously described reports of capecitabine-induced pancreatitis. Clinicians should be aware of this potential adverse effect, particularly in patients with preexisting risk factors for pancreatitis who are prescribed capecitabine.
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PMID:Capecitabine-induced pancreatitis. 1292 Dec 54

In order to identify factors predictive of central nervous system (CNS) metastasis, we reviewed the histories of 579 patients treated with epirubicin-based chemotherapy for metastatic breast cancer. Statistical analysis included Kaplan-Meier survival plots, Cox's regression analysis and competing risk analysis using the cumulative incidence. Median follow-up-time was 137 months (range 0-183+). In this period, one hundred and twenty-four patients (21.4%) developed CNS metastasis. Lung, liver, and lymph node metastases and oestrogen receptor negative or unknown tumor were predictive as well. However, increased pretreatment lactate dehydrogenase (LDH) concentration in serum above the upper normal limits was the strongest single risk factor and should therefore be measured. The risk of CNS metastasis differed considerably among risk groups. Patients without risk factors had a cumulative incidence on 9%, compared to a cumulative incidence of 42%, when the serum LDH concentration was elevated to more than twice the upper normal limits.
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PMID:Predictors of central nervous system metastasis in patients with metastatic breast cancer. A competing risk analysis of 579 patients treated with epirubicin-based chemotherapy. 1595 55

Multidrug resistance remains a major obstacle in the effective treatment of metastatic breast cancer. One mechanism by which multidrug resistance is conferred is the decreased intracellular drug accumulation due to the upregulation of the ATP-binding cassette (ABC) transporters. We have previously demonstrated that jadomycins, polyketide-derived natural products produced by Streptomyces venezuelae ISP5230, inhibit the growth of the human breast ductal carcinoma cell lines T47D and MDA-MB-435. To expand our understanding of jadomycin pharmacology, the goal of the present study was to determine whether the function of ABC efflux transporters affects the anticancer activity of jadomycins to MCF7 breast cancer cells. Seven jadomycin analogs (DNV, B, L, SPhG, F, S, and T) effectively reduced the viability of MCF7 control and ABCB1-, ABCC1-, or ABCG2-overexpressing drug-resistant MCF7 breast cancer cells as measured by methyltetrazolium cell viability assays and lactate dehydrogenase cytotoxicity assays. The inhibition of ABCB1, ABCC1, or ABCG2 with verapamil, MK-571, or Ko-143, respectively, did not augment the cytotoxicity of jadomycins DNV, B, L, SPhG, F, S, or T in drug-resistant MCF7 cells. Furthermore, jadomycins B, L, SPhG, F, S, and T did not increase the intracellular accumulation of ABCB1, ABCC1, or ABCG2 fluorescent substrates in HEK-293 cells stably transfected with ABCB1, ABCC1, or ABCG2. We conclude that jadomycins B, L, SPhG, F, S, and T are effective agents in the eradication of MCF7 breast cancer cells grown in culture, and that their cytotoxicities are minimally affected by ABCB1, ABCC1, and ABCG2 efflux transporter function.
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PMID:Jadomycins are cytotoxic to ABCB1-, ABCC1-, and ABCG2-overexpressing MCF7 breast cancer cells. 2423 27

Liver function tests (LFTs) have been reported as independent predictors of non-liver disease-related morbidity and mortality in general population and cancer patients. In this study, we evaluated the relationship between pretreatment serum LFTs and overall survival (OS) in non-metastatic Caucasian breast cancer patients. Seven LFTs, including albumin, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase (LDH), total bilirubin and total protein, were measured in pretreatment serum from 2425 female Caucasian patients with newly diagnosed, histologically confirmed non-metastatic invasive breast cancer. Multivariate Cox model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) for the association of individual LFTs with 5-year OS while adjusting for age, smoking status, pathological characteristics and treatment regimen. We found that serum albumin, LDH and total bilirubin were significantly associated with 5-year OS in multivariate Cox analyses. Patients with higher albumin level exhibited 45% reduced risk of death (HR = 0.55, 95% CI: 0.40-0.75) compared with those with lower albumin level. Patients with higher total bilirubin level had a nearly 40% reduction in the risk of death (HR = 0.62, 95% CI: 0.45-0.85) and patients with higher LDH levels had a 1.42-fold increased risk of death (HR = 1.42, 95% CI: 1.08-1.88). Furthermore, cumulative analysis showed a significant dose-response trend of significantly increasing risk of death with increasing number of unfavorable LFT levels. Our result highlighted the potential of using pretreatment serum levels of albumin, LDH and total bilirubin as prognostic factors for OS in patients with non-metastatic breast cancer.
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PMID:Prognostic significance of pretreatment serum levels of albumin, LDH and total bilirubin in patients with non-metastatic breast cancer. 2552 24


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