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

The clinical significance of occult micrometastasis (O.M) remains unknown. We investigated it in peripheral blood (P.B.) and bone marrow (B.M.) in breast cancer patients with surgery. First, we investigated the expression levels of 7 representative molecular markers for detecting O.M (CEA, CK-7, CK-18, CK-19, CK-20, MAM and MUC-1) in 27 cancer and 8 non-epithelial cell lines using quantitative RT-PCR (QRT-PCR), and showed that the expression level of CK-7 was higher in every cancer cell line than in the non-epithelial cell lines. Next, we studied the clinical significance of O.M in P.B. and B.M. by QRT-PCR for CK-7 in breast cancer patients with surgery. Based on comparison with 17 non-cancer controls, 37 (18.0%) and 100 (48.5%) of the 206 patients were positive for CK-7 in P.B. and B.M., respectively. In 98 cases observed over 24 months after surgery, the CK-7-positive group in P.B. had poorer disease-free survival (DFS) than the negative group (p<0.01). The CK-7-positive group in P.B. showed poorer DFS than the negative group in 132 lymph node-negative cases (p=0.01), and moreover, in 61 lymph node-negative cases observed over 24 months after surgery, the CK-7-positive group in P.B. showed poorer DFS than the negative group (p<0.0001). In B.M., no significant difference in DFS was found between the CK-7-positive and CK-7-negative groups. QRT-PCR for CK-7 could be a useful and universal method for detecting O.M, and the quantitative detection of CK-7 in P.B. would have a prognostic value as a marker of early recurrence in breast cancer patients with surgery.
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PMID:Detection of occult cancer cells in peripheral blood and bone marrow by quantitative RT-PCR assay for cytokeratin-7 in breast cancer patients. 1570 29

This study compares the sensitivities and specificities of three techniques for the detection of circulating epithelial cells in the blood of patients with breast cancer. The number of circulating epithelial cells present in the blood of 40 patients with metastatic breast cancer and 20 healthy volunteers was determined by: immunomagnetic separation (IMS) and laser scanning cytometry (LSC), cell filtration and LSC and a multimarker real-time RT-PCR assay. Numbers of cytokeratin-positive cells identified and expression of three PCR markers were significantly higher in the blood of patients with breast cancer than in healthy volunteers. Using the upper 95% confidence interval of cells detected in controls to determine positive patient samples: 30% of patients with metastatic breast cancer were positive following cell filtration, 48% following IMS, and 60, 45 and 35% using real-time RT-PCR for cytokeratin 19, mammaglobin and prolactin-inducible peptide. Samples were significantly more likely to be positive for at least one PCR marker than by cell filtration (83 vs 30%, P<0.001) or IMS (83 vs 48%, P<0.001). The use of a multimarker real-time RT-PCR assay was therefore found to be the most sensitive technique for the detection of circulating epithelial cells in the blood of patients with breast cancer.
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PMID:Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques. 1571 2

Persistent high mortality rates in breast cancer patients, in spite of latest advances in diagnosis and therapy, affirm the necessity of new developments in tumor biology prognostic factors. Immunocytochemical detection of disseminated breast cancer cells in bone marrow has been frequently associated with a decrease in disease-free survival as an independent prognostic factor, but methods based on molecular biology procedures must still be validated. Considering tumor heterogeneity, the multimarker approach has been suggested as a better strategy than individual marker assays. The aim of this work was evaluation of the prognostic value of a multimarker reverse-transcriptase polymerase chain reaction (RT-PCR) assay, associating four mRNA markers for the detection of disseminated breast cancer cells. We compared the prognostic significance of cytokeratin 19 (CK19), carcinoembryonic antigen (CEA), mammaglobin (MG) and the mucin MUC5B mRNA in bone marrow aspirates in the follow-up of 80 operable breast cancer patients. The best prognostic value for clinical outcome was seen for CEA mRNA, not improved for any association with other markers. Unexpectedly, some tumor mRNA in bone marrow correlates with a favorable clinical outcome, especially MUC5B. Therefore, our results suggest that not all epithelial or tumor markers have the same significance in predicting the metastatic potential of disseminated cancer cells. New parameters are needed for the identification of individual patients at high risk of tumor recurrence. Multimarker RT-PCR assays could be a good approach, but they should be performed associating mRNA markers that are able to predict tumor aggressiveness associated with poor outcome and not just epithelial markers, which only indicate the mere presence of tumor cells.
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PMID:Clinical evaluation of a panel of mRNA markers in the detection of disseminated tumor cells in patients with operable breast cancer. 1601 42

Sentinel lymph node (SLN) status is highly predictive of overall axillary lymph node involvement in breast cancer. Historically, SLN-positive patients have undergone axillary lymph node dissection in a second surgery. Intraoperative SLN analysis could reduce the cost and complications of a second surgery; however, existing histopathological methods lack standardization and exhibit poor sensitivity. Rapid molecular methods may lead to improved intraoperative diagnosis of SLN metastasis. In this study, we used a genome-wide gene expression analysis of breast and other tissues to identify seven putative markers for detecting breast cancer metastasis. We assessed the utility of these markers for identifying clinically actionable metastases in lymph nodes through reverse transcriptase-polymerase chain reaction analysis of SLNs from 254 breast cancer patients. Polymerase chain reaction signals were compared to pathology on a per-patient basis. The optimal two-gene combination, mammaglobin and cytokeratin 19, detected clinically actionable metastasis in breast SLNs with 90% sensitivity and 94% specificity. Application of stringent criteria for identifying presumptive hematoxylin- and eosin-positive samples increased sensitivity and specificity to 91 and 97%, respectively. This study represents the first comprehensive demonstration of the utility of gene expression markers for detecting clinically actionable breast metastases. An intraoperative molecular assay using these markers has the potential to significantly reduce second surgeries for patients undergoing SLN dissection.
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PMID:Identification and characterization of optimal gene expression markers for detection of breast cancer metastasis. 1604 4

Autocrine motility factor (AMF) stimulates, via an autocrine route, the motility of cancer cells. The current study investigated the expression of AMF and its receptor, AMFR (gp78), in breast cancer and attempted to dissect a clinical link. Breast tumor tissues (n=120) and non-neoplastic normal tissues (n=32) were studied. AMF and AMFR distribution in tissues were assessed using immunohistochemistry and their transcripts were analyzed using RT-PCR and quantitative PCR. Median follow-up of the cohort was 10 years. Normal mammary epithelial cells, but not stromal and endothelial cells, weakly stained for AMF and AMFR. However, cancer cells showed stronger staining. Both AMF and AMFR transcripts were significantly higher in tumor than in normal tissues (p=0.003 and p=0.0001, respectively). High levels of AMF and AMFR were seen in patients who died of breast cancer (p=0.049, p=0.0435) and high AMF was also seen in patients who had local recurrence (p=0.039) compared with those who remained disease free. A significant correlation was seen between long-term survival and the AMFR:CK19 ratio, in which patients with high AMFR:CK19 ratio tumors had a significantly shorter survival (101.0 months, 80.6-121.4) compared with those with low ratio (136.0 months, 123.7-148.2), p=0.0331. In conclusion, AMF and AMFR are overexpressed in human breast cancer and are negatively associated with patients' clinical outcome. This strongly indicates that the AMF-AMFR complex plays an important role in the progression of breast cancer, as well as having a prognostic role.
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PMID:Expression of autocrine motility factor (AMF) and its receptor, AMFR, in human breast cancer. 1620 25

One-hundred twenty-four proteins have been identified in the soluble nuclear protein mixture from MCF-7 human breast cancer cells, of which more than 90% are classically categorized as nuclear proteins. Proteins were also studied from three drug resistant MDF-7 lines, selected previously from the same parent line by exposure to etoposide, to mitoxantrone, or to adriamycin in the presence of verapamil. Both quantitative gel comparisons and stable isotope labeling were used to identify a total of fourteen proteins whose abundances are altered by more than 2-fold in the three resistant lines. Several cytoskeleton proteins, cytokeratin 8, cytokeratin 19, septin 2, and alpha tropomyosin, are decreased in common across the three resistant cell lines. PARP-l (poly[ADP-ribosyl]transefrase or connexion) is found to be less abundant in all three resistant lines. Nucleolin is more abundant in lines resistant to etoposide and mitoxantrone, while the mitotic checkpoint protein BUB 3 is more abundant in the line resistant to adriamycin/verapamil.
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PMID:Proteomic evidence for roles for nucleolin and poly[ADP-ribosyl] transferase in drug resistance. 1621 10

Although long-term clinical use of progestins is associated with an increased incidence of breast cancers, their role in established cancers is unclear. Estrogens are considered to be the main mitogens in the majority of breast cancers. Whether progesterone affects proliferation and/or differentiation is under debate. To assess the role of progesterone in established breast cancers, we used T47D human breast cancer cells that are estrogen receptor (ER) positive and either progesterone receptor (PR) negative or positive for PRA, PRB, or both. These cells were grown as strictly estrogen-dependent solid tumors in ovariectomized female nude mice. Progesterone or medroxyprogesterone acetate (MPA) alone did not support tumor growth, nor did progesterone or MPA given simultaneously with estrogen significantly alter estrogen-dependent tumor growth. However, treatment of mice bearing ER+PR+ but not ER+PR- tumors with either progesterone or MPA increased expression of the myoepithelial cytokeratins (CK) 5 and 6 in a subpopulation of tumor cells. These CK5+/CK6+ cells had decreased expression of luminal epithelial CK8, CK18, and CK19. We conclude that progestins exert differentiative effects on tumors characterized by transition of a cell subpopulation from luminal to myoepithelial. This may not be beneficial, however, because such a phenotype is associated with poor prognosis.
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PMID:Progestins initiate a luminal to myoepithelial switch in estrogen-dependent human breast tumors without altering growth. 1626 99

The objective of this study was mainly to develop and evaluate a membrane array-based method simultaneously detecting the expression levels of a multiple mRNA marker panel in the peripheral blood for used in complementary breast cancer diagnosis. The mRNA markers employed included cytokeratin 19 (CK-19), carcinoembryonic antigen (CEA), c-Met, Her2/neu, and mammaglobin (hMAM). The specimens of peripheral blood were collected from 80 healthy women and 102 female patients with breast cancer. The expression levels of molecular markers were evaluated by real-time Q-PCR and membrane array. Data obtained from real-time Q-PCR and membrane array were subjected to linear regression analysis, revealing that there was a high degree of correlation between the results of these two methods (r=0.979, P<0.0001). The result of membrane array assay with a combined panel of five mRNA markers was demonstrated to achieve sensitivity of 80.6%, and specificity of 83.8% for breast cancer detection, much higher than those of analysis of single marker. In addition, we demonstrated that the membrane array method could detect circulating cancer cells at a density as low as five cancer cells per 1 ml of blood. The analysis of correlation between the outcome of membrane array and clinicopathological characteristics indicated that overexpression of the multiple marker panel was significantly correlated with tumor size (P=0.030) and TNM stage (0.009). In conclusion, the detection of circulating cancer cells by means of membrane array simultaneously monitoring five mRNA markers could significantly enhance the sensitivity and specificity for cancer cell detection.
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PMID:Simultaneous detection of multiple mRNA markers CK19, CEA, c-Met, Her2/neu and hMAM with membrane array, an innovative technique with a great potential for breast cancer diagnosis. 1628 46

The presence of metastases in lymph nodes is the most powerful prognostic factor in breast cancer patients. Routine histological examination of lymph nodes has limited sensitivity for the detection of breast cancer metastases. The aim of the present study was to develop a multimarker reverse transcriptase-polymerase chain reaction (RT-PCR) assay for the detection of minimal residual disease in sentinel nodes of breast cancer patients. RNA was extracted from 30 sentinel lymph nodes (SLN) obtained from 28 patients, three primary breast cancers (positive controls), three lymph nodes from patients with benign diseases, and peripheral blood lymphocytes of 10 healthy volunteers (negative controls). RT-PCR was performed using the following markers; cytokeratin (CK)-19, NY-BR-1 and mammaglobin B. RT-PCR results were compared to enhanced histopathologic examination and immunohistochemistry (IHC). All three positive controls showed strong PCR amplification for all three markers. None of the 13 negative controls was amplified by any of the three markers. Among the 30 SLN analysed, breast cancer metastases were detected in six SLNs by routine histology, in eight by IHC and in 15 by RT-PCR. We conclude that a multimarker RT-PCR assay probing for NY-BR-1, mammaglobin-B, and CK-19 is more sensitive compared to enhanced pathologic examination. This method may prove to be of value in breast cancer staging and prognosis evaluation.
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PMID:Multimarker RT-PCR assay for the detection of minimal residual disease in sentinel lymph nodes of breast cancer patients. 1667 Jul 23

We report the establishment of a breast epithelial cell model that undergoes growth arrest at different stages of the cell cycle depending upon the DNA damaging agents encountered. Primary breast epithelial cells from normal reductive mammoplasty were grown in low-calcium culture medium. Free-floating cells under this condition were separated and used for establishment of the MCF-15 breast epithelial cell line. We found that MCF-15 breast epithelial cells display a superb response to different phases of the cell cycle arrest in response to various DNA damaging agents. Immunohistological analysis indicates that MCF-15 cells express cytokeratin 19, CD44, CXCR4, SDF-1, SPARC and vimentin. Although less than 5% of the MCF-15 cells expressed Muc-1 in culture, increased Muc-1 expression was observed in luminal epithelial cells along the newly formed lumen in xenografts. Furthermore, a small population of MCF-15 cells expressed estrogen receptor-alpha (ERalpha) in xenografts while ERalpha expression was not detected in monolayer culture. Therefore, the MCF-15 breast epithelial cell line possesses characteristics of breast progenitor cells and provides a good cell culture model for studying the response to DNA damage and the etiology of aggressive basal-like breast cancers.
Breast Cancer Res Treat 2006 Aug
PMID:Isolation and characterization of a breast progenitor epithelial cell line with robust DNA damage responses. 1654 20


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