Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many serological markers have been utilized to indicate the status, risk, or presence of breast cancer. In May 1996, the American Society of Clinical Oncology (ASCO) convened a Tumor Marker Panel and determined clinical practice guidelines for the use of tumor markers in breast cancer. Eight markers containing carcinoembryonic antigen (CEA) and CA15-3 were evaluated and assigned by expert reviewers to be valuable markers of breast cancer. CA15-3 recognizes a mucin-like glycoprotein, MUC-1, which is frequently expressed in breast cancer tissues. BCA225, which may recognize antigens similar to MUC-1 glycoprotein, are sensitive and specific markers for breast cancer. However, it is not recommended to measure the 2 markers in combination. The measurement of carboxy-terminal telopeptide of type I collagen (I CTP) is worthwhile as a serological diagnostic method of bone metastasis from breast cancer. Other markers such as erbB-2, CYFRA 21-1 and PTHrP are candidates for clinical utilization as tumor markers in breast cancer.
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PMID:[Tumor markers in breast cancer]. 1147 35

Histological detection of axillary lymph node metastases is still the most valuable prognostic parameter for breast cancer, but about 30% of node-negative patients relapse within five years, suggesting that current methods are inadequate for identifying metastatic disease. More sensitive, PCR-based methods for the detection of metastatic cells are now available, enabling the amplification of cancer cell-specific mRNA messages by the RT-PCR assay. An ideal tumour marker, consistently expressed in tumour samples and not at all in normal lymph nodes, remains to be identified. The present study first investigated the expression of seven mRNA markers, CEA, CK19, c-Met, mammaglobin, MUC-1, beta1-->GalNAc-T and p97, selected on the basis of their previously reported specificity for breast cancer cells. Eighteen lymph nodes were examined from patients without tumours. Only mammaglobin mRNA and CEA mRNA were not expressed in normal nodes. All of the other markers showed a band of expression in 17%-55% of cases, indicating that they are not breast cancer-specific. CEA mRNA and mammaglobin mRNA expression could be detected in 15/20 (75%) and 19/20 (95%) primary breast carcinomas, respectively. The expression of mammaglobin mRNA and CEA mRNA was then compared in axillary lymph nodes from 248 consecutive breast cancer patients, 89 with histologically documented lymph node metastasis and 159 without histological evidence of metastatic disease. Ninety-seven per cent of the patients with histologically involved nodes showed expression of mammaglobin mRNA, whereas CEA mRNA was expressed in 79% of these cases. In the group of patients with histologically negative lymph nodes, 46 (29%) and 32 (20%) were found to be positive for mammaglobin and CEA expression, respectively, indicating the presence of metastases not detected by routine histological examination of one lymph node section. These results show that both mammaglobin RT-PCR and CEA RT-PCR are useful tools for the detection of breast cancer metastases in axillary lymph nodes. The detection sensitivity of the mammaglobin RT-PCR is far superior to that of the CEA RT-PCR, allowing the diagnosis of occult metastases in nearly one-third of cases.
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PMID:mRNA markers of breast cancer nodal metastases: comparison between mammaglobin and carcinoembryonic antigen in 248 patients. 1159 97

Human epidermal growth factor receptor 2 (p185 HER2) oncoprotein immunohistochemical expression and DF3 antigen distribution were evaluated in 129 patients with primary breast cancer. p185 HER2 overexpession was positively correlated with the degree of differentiation, metastatic disease, progesterone receptors, and cytoplasmic distribution of DF3 antigen. p185 HER2 overexpression had prognostic significance for the disease-free interval.
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PMID:Immunohistochemical study of p185 HER2 and DF3 in primary breast cancer and correlation with CA-15-3 serum tumor marker. 1186 May 39

Mucin glycoproteins on breast cancer cells carry shortened carbohydrate chains. These partially deglycosylated mucin 1 (MUC-1) structures are recognized by the monoclonal antibody SM3, which is being tested for its diagnostic utility. We used NMR spectroscopy to analyze the binding mode and the binding epitope of peptide and glycopeptide antigens to the SM3 antibody. The pentapeptide PDTRP and the glycopentapeptide PDT(O-alpha-D-GalNAc)RP are known ligands of the monoclonal antibody. The 3D structures of the ligands in the bound conformation were determined by analyzing trNOESY build-up rates. The peptide was found to adopt an extended conformation that fits into the binding pocket of the antibody. The binding epitopes of the ligands were determined by saturation transfer difference (STD) NMR spectroscopy. The peptide's epitope is predominantly located in the N-terminal PDT segment whereas the C-terminal RP segment has fewer interactions with the protein. In contrast, the glycopeptide is interacting with SM3 utilizing all its amino acids. Pro1 shows the strongest binding effect that slightly decays towards Pro5. The GalNAc residue interacts mainly via the N-acetyl residue while the other protons show less interactions similar to that of Pro5. The glycopeptide in the bound state also has an extended conformation of the peptide with the carbohydrate oriented towards the N-terminus. Docking studies showed that peptide and glycopeptide fit the binding pocket of the mAb SM3 very well.
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PMID:NMR-based determination of the binding epitope and conformational analysis of MUC-1 glycopeptides and peptides bound to the breast cancer-selective monoclonal antibody SM3. 1187 59

MUC1 mucin is aberrantly expressed in many epithelial malignancies and is a promising tumor antigen for target-directed immunotherapy against human breast cancer. Mycobacterium BCG is an effective immunoadjuvant which is known to induce Th1 immune response. Recombinant BCG expressing tumor antigen and secreting cytokine may therefore potentiate the tumor antigen-specific immune responses. In this study, we constructed a recombinant BCG-MUC1-IL2, which expresses a high level of human MUC1 VNTR core protein and secretes functional interleukin 2 (IL2). The immune responses induced by BCG-MUC1-IL2 were examined using a SCID mouse model reconstituted with immunologically competent human lymphocytes, SCID/hu-PBL. The mucin-specific IFN-gamma was secreted only by the lymphocytes derived from animals immunized with BCG-MUC1-IL2, but not with BCG-vector or purified mucin protein for the vaccination. In contrast, in vitro secretion of IL4 by the immunized lymphocytes was only seen in the group of animals which received native MUC1 protein, but not BCG-MUC1-IL2 and BCG-vector. Minimal MUC1-specific IgG and IgM were detected in SCID/hu-PBL mice vaccinated with BCG-MUC1-IL2. These results suggest that BCG-MUC1-IL2 preferentially induces MUC1-specific cellular immune responses and it may serve as a vaccine for breast cancer prevention and treatment.
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PMID:Induction of MUC1-specific cellular immunity by a recombinant BCG expressing human MUC1 and secreting IL2. 1201 14

Emerging high-throughput screening technologies are rapidly providing opportunities to identify new diagnostic and prognostic markers and new therapeutic targets in human cancer. Currently, cDNA arrays allow the quantitative measurement of thousands of mRNA expression levels simultaneously. Validation of this tool in hospital settings can be done on large series of archival paraffin-embedded tumor samples using the new technique of tissue microarray. On a series of 55 clinically and pathologically homogeneous breast tumors, we compared for 15 molecules with a proven or suspected role in breast cancer, the mRNA expression levels measured by cDNA array analysis with protein expression levels obtained using tumor tissue microarrays. The validity of cDNA array and tissue microarray data were first verified by comparison with quantitative reverse transcriptase-polymerase chain reaction measurements and immunohistochemistry on full tissue sections, respectively. We found a good correlation between cDNA and tissue array analyses in one-third of the 15 molecules, and no correlation in the remaining two-thirds. Furthermore, protein but not RNA levels may have prognostic value; this was the case for MUC1 protein, which was studied further using a tissue microarray containing approximately 600 tumor samples. For THBS1 the opposite was observed because only RNA levels had prognostic value. Thus, differences extended to clinical prognostic information obtained by the two methods underlining their complementarity and the need for a global molecular analysis of tumors at both the RNA and protein levels.
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PMID:Distinct and complementary information provided by use of tissue and DNA microarrays in the study of breast tumor markers. 1236 96

Human mucin 1 (MUC1) is an epithelial mucin glycoprotein that is overexpressed in 90% of all adenocarcinomas including breast, lung, pancreas, prostate, stomach, colon, and ovary. MUC1 is a target for immune intervention, because, in patients with solid adenocarcinomas, low-level cellular and humoral immune responses to MUC1 have been observed, which are not sufficiently strong to eradicate the growing tumor. The hypothesis for this study is that enhancing MUC1-specific immunity will result in antitumor immunity. To test this, the authors have developed a clinically relevant breast cancer model that demonstrates peripheral and central tolerance to MUC1 and develops spontaneous tumors of the mammary gland. In these mice, the authors tested a vaccine formulation comprised of liposomal-MUC1 lipopeptide and human recombinant interleukin-2. Results indicate that when compared with untreated mice, immunized mice develop T cells that express intracellular IFN-gamma, are reactive with MHC class I H-2Db/MUC1 tetramer, and are cytotoxic against MUC1-expressing tumor cells in vitro. The presence of MUC1-specific CTL did not translate into a clinical response as measured by time of tumor onset, tumor burden, and survival. The authors demonstrate that some of the immune-evasion mechanisms used by the tumor cells include downregulation of MHC-class I molecule, expression of TGF-beta2, and decrease in IFN-gamma -expressing effector T cells as tumors progress. Finally, utilizing an injectable breast cancer model, the authors show that targeting a single tumor antigen may not be an effective antitumor treatment, but that immunization with dendritic cells fed with whole tumor lysate is effective in breaking tolerance and protecting mice from subsequent tumor challenge. A physiologically relevant spontaneous breast cancer model has been developed to test improved immunotherapeutic approaches.
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PMID:Mucin 1-specific immunotherapy in a mouse model of spontaneous breast cancer. 1251 29

The study of different epithelial antigen expression has been performed in 183 breast cancers. In 73 patients regional lymph nodes were studied as well. Panepithelial antigen Egp-34 (Mab HEA-125) was expressed in 100% of primary tumors and metastases. Antigen MUC-1 (Mab ICO-25) was identified in 93% of breast cancers. Monomorphic type of expression in tumor cells was typical for Egp-34, MUC-1 being in certain cases expressed as a proportion of cells. Additional immunohistochemical study of regional lymph nodes with Mab to Egp34 and MUC-1 provides a 10% increase in the rate of breast cancer metastases detection compared to histological examination alone. The carcinoembryonic antigen (CEA) was useful in identification of metastases only in CEA-positive breast cancers.
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PMID:[The role of epithelial antigens in diagnosis and staging of breast cancer]. 1253 20

Genetically modified mice with spontaneous development of mammary carcinoma provide a powerful tool to study the efficacy of tumor vaccines, since they mimic breast cancer development in humans. We used a transgenic murine model expressing polyomavirus middle T oncogene and mucin 1 tumor-associated Ag to determine the preventive effect of a dendritic/tumor fusion cell vaccine. The MMT (a transgenic murine model) mice developed mammary carcinoma between the ages of 65-108 days with 100% penetrance. No spontaneous CTL were detected. However, prophylactic vaccination of MMT mice with dendritic/tumor fusion cells induced polyclonal CTL activity against spontaneous mammary carcinoma cells and rendered 57-61% of the mice free of the disease at the end of experiment (180 days). Furthermore, the level of CTL activity was maintained with multiple vaccinations. The antitumor immunity induced by vaccination with dendritic/tumor fusion cells reacted differently to injected tumor cells and autochthonous tumor. Whereas the injected tumor cells were rejected, the autochthonous tumor evaded the attack and was allowed to grow. Collectively these results indicate that prophylactic vaccination with dendritic/tumor fusion cells confers sufficient antitumor immunity to counter the tumorigenesis of potent oncogenic products. The findings in the present study are highly relevant to cancers in humans.
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PMID:Prevention of spontaneous breast carcinoma by prophylactic vaccination with dendritic/tumor fusion cells. 1257 67

Mucin-1 (MUC-1) is a high-molecular-weight glycoprotein rich in serine and threonine residues that are O-glycosylated. Expression of MUC-1 is increased in breast, ovarian, and other adenocarcinomas, and altered glycosylation results in exposure of novel peptide epitopes and the expression of tumor-associated carbohydrate residues, such as Thomsen-Freidenreich and sialyl-Tn (STn) antigens. Preclinical studies suggested that induction of immune response to tumor-associated carbohydrate moieties results in inhibition of tumor growth. A synthetic STn-keyhole limpet hemocyanin (KLH) vaccine (Theratope) is currently being evaluated in clinical trials as active specific immunotherapy in the treatment of advanced breast cancer. Two phase II trials in 50 breast cancer patients compared the STn-KLH vaccine with and without a single low-dose infusion of cyclophosphamide used as an immunomodulator prior to initiation of treatment. Humoral immune responses were higher in patients who had received low-dose cyclophosphamide intravenously (I.V.) compared with patients who had received no cyclophosphamide or oral cyclophosphamide. There was a statistically significant survival difference between all patients treated with the STn-KLH vaccine (overall median survival, 19.1 months; n = 50) and the retrospective control patients (overall median survival, 9.2 months; n = 104). Furthermore, patients who received cyclophosphamide I.V. prior to the STn-KLH vaccine had median survival rates close to 3 times that of patients in a retrospective, frequency-matched, control group who received conventional therapies (cyclophosphamide-I.V. group, 26.5 months vs. 9.2 months, control group). The trials reported minimal toxicity profile with local reactions in the injection site and some flu-like symptoms. On the basis of the phase II trial results, a phase III clinical trial of the STn-KLH vaccine is underway. The trial was closed to enrollment in March 2001 with the accrual of 1030 women. The final analysis is event driven and is expected to commence mid 2003.
Clin Breast Cancer 2003 Feb
PMID:Rationale for the clinical development of STn-KLH (Theratope) and anti-MUC-1 vaccines in breast cancer. 1262 Jan 50


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