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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This conference concerned hereditary cancers of the breast, ovary, and colon, which are the common, often fatal, cancers with the greatest heritability in their causation. Four genes whose mutations impart dominantly heritable predisposition to one or more of these cancers have been cloned and one more has been mapped. The most molecular details are known for colon cancer. The APC gene of familial polyposis coli leads to the accumulation of numerous polyps, but the probability of transformation of the latter to cancer is low. This provides the opportunity to monitor putative preventive measures with an intermediate end point. In hereditary nonpolyposis colon cancer, transformation of the polyp to cancer is accelerated by an inherited mutation in either of two DNA mismatch repair genes. The discovery of an intermediate end point could be very helpful for breast cancer. Testing persons at risk for predisposing mutations depends heavily on the availability of promising measures for prevention or treatment.
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PMID:Hereditary cancers: from discovery to intervention. 857 54

Oncogene is not categorized as a tumor marker in a strict sense, however, cancer related oncogens play an important role as a biomarker in hereditary malignant tumors in a wide sense. Various suppressor oncogenes have been identified in the autosomal dominant hereditary diseases such as APC, in familial adenomatous polyposis, p53 in Li-Fraumeni syndrome and BRACA 1 and 2 in breast cancer. By identifying the mutation site or deletions of germ line, it is possible to make a presymptomatic diagnosis of those hereditary malignant tumors. There is splendid progress in understanding of DNA repair mechanism. Recently, the mismatch repair genes were cloned as a causing gene of HNPCC. There are another group of genes called nucleotide excision repair genes which are causative genes of various autosomal recessive hereditary diseases such as xeroderama pigmentation. Pro and cons of presymptomatic diagnosis of familial adenomatous polyposis were discussed in a series of 72 patients among 42 family trees.
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PMID:[Role of tumor marker in the presymptomatic diagnosis of hereditary malignant tumors]. 869 15

Cancer is often associated with abnormal activation of coagulation leading to a prothrombotic state. Some chemotherapeutic agents used for cancer may induce thrombosis but their biological alterations in the hemostatic system are not yet well understood. This study evaluated alterations of coagulative and fibrinolytic parameters following chemotherapy. In plasma samples of 38 patients (median age: 49 years) receiving CMF (schedule 1-21 or 1-8) for Stage II breast cancer, we evaluated: PT, aPTT, antithrombin III (AT-III), protein C (PC), protein S (PS), thrombin-antithrombin complex (TAT), prothrombin fragment F 1 + 2 (F 1 + 2), fibrinogen (Fbg), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor (PAI-1) and D-dimer (D-D). PT, aPTT, and Fbg were determined with routine methods; AT-III, PC, and PS were measured with coagulative tests; PC and PS were also evaluated with immunoenzymatic methods, t-PA, PAI-1, D-D, TAT, and F 1 + 2 were measured with immunoenzymatic methods. All tests were performed immediately before starting therapy and after each cycle. A PC antigen decrease appeared soon after beginning therapy and lasted throughout chemotherapy. The lowest values were present after the first treatment both in the CMF 1-21 group (mean +/- SD = 72.5 +/- 10.8%) and in the CMF 1-8 group (mean +/- SD = 77.2 +/- 6.9%): PC activity was also decreased. PS antigen decreased after the first administration (mean +/- SD = 73.3 +/- 10% in CMF 1-21 group, and 72.5 +/- 4.9% in CMF 1-8 group): PS activity also decreased. PAI-1 antigen levels increased (mean +/- SD = 43.1 +/- 20.4 ng/ml in the CMF 1-21 group, and 37.5 +/- 12.2 ng/ml in CMF 1-8 group) lasting up to the last cycle. CMF provokes a trend toward hypercoagulability; this effect should be considered when chemotherapy is employed in advanced cancer patients at high risk for thrombosis, or in patients with other risk factors.
Breast Cancer Res Treat 1996
PMID:A prothrombotic state in breast cancer patients treated with adjuvant chemotherapy. 887 81

The detection of inactivating mutations in tumor suppressor genes is critical to their characterization, as well as to the development of diagnostic testing. Most approaches for mutational screening of germ-line specimens are complicated by the fact that mutations are heterozygous and that missense mutations are difficult to interpret in the absence of information about protein function. We describe a novel method using Saccharomyces cerevisiae for detecting protein-truncating mutations in any gene of interest. The PCR-amplified coding sequence is inserted by homologous recombination into a yeast URA3 fusion protein, and transformants are assayed for growth in the absence of uracil. The high efficiency of homologous recombination in yeast ensures that both alleles are represented among transformants and achieves separation of alleles, which facilitates subsequent nucleotide sequencing of the mutated transcript. The specificity of translational initiation of the URA3 gene leads to minimal enzymatic activity in transformants harboring an inserted stop codon, and hence to reliable distinction between specimens with wild-type alleles and those with a heterozygous truncating mutation. This yeast-based stop codon assay accurately detects heterozygous truncating mutations in the BRCA1 gene in patients with early onset of breast cancer and in the APC gene in patients with familial adenomatous polyposis. This approach offers a rapid and reliable method for genetic diagnosis in individuals at high risk for germ-line mutations in cancer susceptibility genes.
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PMID:Detection of heterozygous truncating mutations in the BRCA1 and APC genes by using a rapid screening assay in yeast. 912 15

Breast cancer disease and as well as CMF-chemotherapy are associated with an increased risk for thromboembolic complications. There is evidence that effects on the hemostatic system may play an important role. To minimize the impact of tumor associated hypercoagulability, we choose to study CMF-associated effects on the hemostatic system within an adjuvant setting. Blood coagulation and fibrinolysis were examined before and 24 hours after intravenous application of CMF-therapy at 17 patients with breast cancer. 16 parameters of coagulation and fibrinolysis were studied. In a longitudinal analysis covering the complete 6 month treatment period we found a decrease of thromboplastin time (TPZ) factor VII (FVII) and protein C antigen (PC Ag) and activity (PC Act). Clinically relevant pathological results and cumulative effects were observed only for PC Ag and Act, while the mean values of TPZ and FVII returned to pre-treatment levels after each course of treatment. These data suggest a potential impact of CMF-chemotherapy on synthesis and activation of vitamin-K-dependent coagulation factors thus providing a possible explanation for the increased risk for thrombosis during CMF-chemotherapy.
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PMID:[Adjuvant CMF chemotherapy in patients with breast cancer--results on blood coagulation and fibrinolysis]. 928 Dec 54

The problem of interpreting missense mutations of disease-causing genes is an increasingly important one. Because these point mutations result in alteration of only a single amino acid of the protein product, it is often unclear whether this change alone is sufficient to cause disease. We propose a Bayesian approach that utilizes genetic information on affected relatives in families ascertained through known missense-mutation carriers. This method is useful in evaluating known disease genes for common disease phenotypes, such as breast cancer or colorectal cancer. The posterior probability that a missense mutation is disease causing is conditioned on the relationship of the relatives to the proband, the population frequency of the mutation, and the phenocopy rate of the disease. The approach is demonstrated in two cancer data sets: BRCA1 R841W and APC I1307K. In both examples, this method helps establish that these mutations are likely to be disease causing, with Bayes factors in favor of causality of 5.09 and 66.97, respectively, and posterior probabilities of .836 and .985. We also develop a simple approximation for rare alleles and consider the case of unknown penetrance and allele frequency.
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PMID:Missense mutations in disease genes: a Bayesian approach to evaluate causality. 958 99

Thromboembolic complications and decrease in protein C and S have been observed in patients while receiving combination chemotherapy for breast cancer. We investigated whether initial cytotoxic treatment of non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) is also associated with changes in these anticoagulant parameters. For this purpose 25 patients with intermediate to high grade NHL and seven with HD, undergoing primary treatment with cytotoxic drugs were evaluated at three time-points: pre-therapy, mid-therapy and post-therapy. In contrast to the breast cancer patients, no significant changes in protein C, protein S and antithrombin III levels were observed in the NHL patients during the various stages of therapy. However in HD patients, the mean protein C values had a tendency to be higher at mid-therapy compared to pre-therapy and protein S levels had a tendency to be higher at mid-therapy compared to post-therapy. In lymphoma patients receiving primary cytotoxic treatment we did not find changes in anticoagulant parameters that can explain a chemotherapy-induced hypercoagulable state, as has been reported in breast cancer patients.
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PMID:Levels of proteins C and S do not decline subsequent to first line chemotherapy in lymphoma patients. 960 Jan 11

Recently, a T-to-A transversion creating an 8-base mononucleotide tract in the APC gene, resulting in substitution of lysine for isoleucine at codon 1307 (I1307K), was found in a subset of Ashkenazi Jews. This sequence variant was most frequent in colorectal cancer patients with a positive family history of colorectal cancer. To determine whether the I1307K variant plays a role in colorectal or breast cancer predisposition in the Norwegian population, we have analyzed blood samples from 210 colorectal cancer patients and 183 breast cancer patients by PCR and direct sequencing. Thirty-seven of the colorectal cancer patients had a positive family history of cancer. Among the breast cancer patients, 24 had a family history of colorectal cancer and 75 a family history of breast and/or ovarian cancer. Only one colorectal cancer patient who belonged to a Jewish family was found to carry the A variant. Our data show that the I1307K variant is rare in the Norwegian population and should not be viewed as a candidate for susceptibility testing for colorectal cancer.
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PMID:The APC gene I1307K variant is rare in Norwegian patients with familial and sporadic colorectal or breast cancer. 967 46

Subsets of patients with common cancers belong to families in which the predisposition is inherited in a regular Mendelian fashion. Genes underlying these cancers are now recognized in colorectal cancer (APC, mismatch repair genes, LKB1) and in breast cancer (BRCA1, BRCA2) whereas, in prostate cancer, a locus in chromosome 1 (HPC1) has been proposed on the basis of linkage analysis. Major challenges are to determine the population incidence of these mutations, their penetrance, phenotypic expression, and the effects of modifier genes and epigenetic factors. Finally, the role of encoded proteins in carcinogenesis is a matter of major interest.
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PMID:The genetics of hereditary common cancers. 969 Sep 90

Potential effects of tamoxifen therapy on blood coagulation and fibrinolysis were investigated in women with breast cancer. We studied 14 parameters of hemostasis in 19 postmenopausal women receiving 20 mg tamoxifen/day as an adjuvant treatment. Blood sampling was done before and after the 1st, 3rd, and 6th month of treatment. Pretreatment values of procoagulation, anticoagulation, plasminogen, and plasminogen activator inhibitor were found within the reference range, whereas tissue-plasminogen activator, fibrin degradation products, and prothrombin-fragment 1+2 were elevated. On therapy an initial decrease of all measured parameters was observed. The effect was pronounced in coagulation inhibitors (antithrombin III, protein C and S). No pathological values (below 60%) were observed. No further effects were found during the 3rd and 6th month of treatment. Our data indicate that the decrease of hemostatic parameters during the initial phase of tamoxifen treatment is due to the timing of blood collection, which took place no more than 14 days after surgery. The reduction of coagulation inhibitors was not associated with pathological values. No cumulative effects were seen during tamoxifen therapy. The decrease was not associated with a concomittant increase of in vivo coagulation markers (prothrombin-fragment 1+2, thrombin-antithrombin-complex, fibrin degradation products). Therefore our results are likely to reflect only the resolution of postoperative activation and do not translate into a drug related thrombogenic effect.
Breast Cancer Res Treat 1998 Jul
PMID:Adjuvant antiestrogen treatment with tamoxifen in postmenopausal women with breast cancer: a longitudinal study of blood coagulation and fibrinolysis. 980 22


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