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

When defined in terms of markers for normal cell lineages, most invasive breast cancer cells correspond to the phenotype of the common luminal epithelial cell found in the terminal ductal lobular units. Luminal epithelial cells cultured from milk, which have limited proliferative potential, have now been immortalized by introducing the gene encoding simian virus 40 large tumor (T) antigen. Infection with a recombinant retrovirus proved to be 50-100 times more efficient than calcium phosphate transfection, and of the 17 cell lines isolated, only 5 passed through a crisis period as characterized by cessation of growth. When characterized by immunohistochemical staining with monoclonal antibodies, 14 lines showed features of luminal epithelial cells and of these, 7 resembled the common luminal epithelial cell type in the profile of keratins expressed. These cells express keratins 7, 8, 18, and 19 homogeneously and do not express keratin 14 or vimentin; a polymorphic epithelial mucin produced in vivo by luminal cells is expressed heterogeneously and the pattern of fibronectin staining is punctate. Although the cell lines have a reduced requirement for added growth factors, they do not grow in agar or produce tumors in the nude mouse. When the v-Ha-ras oncogene was introduced into two of the cell lines by using a recombinant retrovirus, most of the selected clones senesced, but one entered crisis and emerged after 3 months as a tumorigenic cell line.
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PMID:Efficient immortalization of luminal epithelial cells from human mammary gland by introduction of simian virus 40 large tumor antigen with a recombinant retrovirus. 170 84

Experimental systems using human mammary tissue, secretions and tumours may be based on in vitro culture or on growth of tissue or tumour fragments in the nude mouse. In the development of in vitro culture systems, a detailed characterization of the cultured cells within the framework of the epithelial cell lineages found in vivo is crucial. Monoclonal antibodies are useful tools for defining the profile of antigens expressed by the basal and luminal cells in the normal gland and in distinguishing subclasses between these two major groups. When these same reagents are used to characterize breast cancers, the majority are found to show the phenotype of luminal cells, with a small subset showing some evidence of basal markers. Luminal epithelial cells cultured from milk or reduction mammoplasty tissue have a short life span in vitro but can be immortalized using SV40TAg. Demonstrably malignant cells are difficult to culture from primary breast cancer, but ER+ and ER- cell lines showing the luminal phenotypes have been readily developed from metastases: some ER- breast cancer cell lines show a more undifferentiated phenotype, and these may have developed from tumours expressing basal markers. As with in vitro culture, it is difficult to obtain tumour growth in the nude mouse from primary breast cancer specimens, and established cell lines are also difficult to grow in this animal. We have focused our studies on cell lines with the luminal phenotype developed from milk. These non-tumorigenic cell lines differ from breast cancer cell lines (a) in being able to form organized three dimensional structures in the presence of an extracellular matrix and (b) in the correct glycosylation of the polymorphic epithelial mucin, which is expressed and aberrantly glycosylated in cancers. These cell lines are therefore being used to study the mechanisms underlying morphogenesis and the processing of PEM, and also as recipients for oncogenes and proto-oncogenes.
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PMID:Human models of breast cancer. 834 39

The comparative uterotrophic responses of ovariectomized Wistar (Han) rats to tamoxifen, toremifene, and 17beta-estradiol have been determined over a period of 72 h. Uterine wet weight; luminal epithelial cell hypertrophy; and BrdU labeling index in the different tissue compartments of the uterus, and the immunohistochemical expression of nuclear estrogen receptor alpha (nERalpha), and nuclear progesterone receptor (nPR) were examined. Luminal epithelial cell hypertrophy was produced by all three compounds to a similar degree. 17beta-Estradiol produced an increase in uterine wet weight due to fluid imbibition over the 3-day period, and an increase in DNA synthesis in the endometrial stromal and myometrial compartments of the uterus, as measured by increased BrdU incorporation. Estradiol increased the expression of nERalpha and nPR in the myometrium with time and decreased nERalpha levels from the overexpressed levels in control ovariectomized rat luminal epithelial cells. Tamoxifen and toremifene caused a smaller increase in uterine weight and the BrdU labeling index in the endometrial stroma and myometrium than did estradiol, and they increased the expression of nERalpha and nPR in the myometrium. Tamoxifen and toremifene differed from estradiol in that they did not decrease the expression of nERalpha in the luminal epithelial cells of the uterus. The response of PR expression was the same for tamoxifen, toremifene, and estradiol, and was therefore considered to be the most reliable indication of an estrogen-agonist effect in this study. The ability to distinguish differential, compartmentalized effects for agonists of estrogen action in the uterus will allow a better risk assessment for new pharmaceuticals that are used as breast cancer chemotherapeutic agents, especially where their use may also be associated with an increased risk of uterine cancers, in particular.
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PMID:Compartmentalized uterotrophic effects of tamoxifen, toremifene, and estradiol in the ovariectomized Wistar (Han) rat. 1035 11

Recent microarray studies have identified distinct subtypes of breast tumors that arise from different cell types and that show statistically significant differences in patient outcome. To gain insight into these differences, we identified in vitro and in vivo changes in gene expression induced by chemotherapeutics. We treated two cell lines derived from basal epithelium (immortalized human mammary epithelial cells) and two lines derived from luminal epithelium (MCF-7 and ZR-75-1) with chemotherapeutics used in the treatment of breast cancer and assayed for changes in gene expression using DNA microarrays. Treatment doses for doxorubicin and 5-fluorouracil were selected to cause comparable cytotoxicity across all four cell lines. The dominant expression response in each of the cell lines was a general stress response; however, distinct expression patterns were observed. Both cell types induced DNA damage-response genes such as p21(waf1), but the response in the luminal cells showed higher fold changes and included more p53-regulated genes. Luminal cell lines repressed a large number of cell cycle-regulated genes and other genes involved in cellular proliferation, whereas the basal cell lines did not. Instead, the basal cell lines repressed genes that were involved in differentiation. These in vitro responses were compared with expression responses in breast tumors sampled before and after treatment with doxorubicin or 5-fluorouracil/mitomycin C. The in vivo data corroborated the cell-type-specific responses to chemotherapeutics observed in vitro, including the induction of p21(waf1). Similarities between in vivo and in vitro responses help to identify important response mechanisms to chemotherapeutics.
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PMID:Cell-type-specific responses to chemotherapeutics in breast cancer. 1520 34

Metastatic breast cancer involving the hepatobiliary tract or ascites secondary to peritoneal carcinomatosis has been well described. Luminal gastrointestinal tract involvement is less common and recognition of the range of possible presentations is important for early and accurate diagnosis and treatment. We report 6 patients with a variety of presentations of metastatic breast cancer of the luminal gastrointestinal tract. These include oropharyngeal and esophageal involvement presenting as dysphagia with one case of pseudoachalasia, a linitis plastica-like picture with gastric narrowing and thickened folds, small bowel obstruction and multiple strictures mimicking Crohn's disease, and a colonic neoplasm presenting with obstruction. Lobular carcinoma, representing only 10% of breast cancers is more likely to metastasize to the gastrointestinal tract. These patients presented with gastrointestinal manifestations after an average of 9.5 years and as long as 20 years from initial diagnosis of breast cancer. Given the increased survival of breast cancer patients with current therapeutic regimes, more unusual presentations of metastatic disease, including involvement of the gastrointestinal tract can be anticipated.
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PMID:Metastatic breast cancer to the gastrointestinal tract: a case series and review of the literature. 1703

Malignant breast tumors display a wide variety of clinical and pathological features. The rapid development of molecular technologies over the last decade, using micro-array and expression studies to assess human diseases, has revolutionized the field of breast cancer characterization. The technique is based on simultaneous assessment of thousands of genes used to define the metabolic status of tumor cells and their active interaction with the microenvironment. Using hierarchal clustering to profile tumors according to expression of intrinsic genes, locally advanced breast cancers were classified into several major sub-groups, including: 1. Luminal-epithelial group (with sub-classification into types A and B), characterized by expression of the estrogen receptor and genes associated with the estrogenic function; 2. Basal-epithelial group, typically negative for the estrogen and progesterone receptors and the Her2/neu oncogene; 3. ERBB2+ group associated with over expression of the Her2 amplicone; 4. Normal breast-like group. Those sub-groups are the results of different pathophysiological processes, and their clinical outcomes are unique and predictable. Using supervised analysis, in which clinical outcome is pre-defined, several "poor prognostic expression signatures" were found to be associated with an increased risk of relapse, including: a 70-gene cluster in young patients with node-negative tumors, expression signature characteristic of the wound-response activity in node-positive and/or negative tumors, and the Oncotype DX system relevant for risk stratification and systemic treatment recommendations in node-negative receptor-positive tumors. Benefits and limitations of those methods and future directions are discussed.
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PMID:[Molecular portrait of breast cancer with sub-classification of breast tumor]. 1729 49

Molecular profiling has provided biological evidence for the heterogeneity of breast cancer through the identification of intrinsic subtypes like Luminal A, Luminal B, HER2+/ER- and basal-like. It has also led to the development of clinically applicable gene expression-based prognostic panels like the Mammaprint and Oncotype Dx. The increasingly sophisticated understanding allowed by this and similar technology promises future individualized therapy.
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PMID:Molecular profiling in breast cancer. 1746 66

Risk factors for the newly identified "intrinsic" breast cancer subtypes (luminal A, luminal B, basal-like and human epidermal growth factor receptor 2-positive/estrogen receptor-negative) were determined in the Carolina Breast Cancer Study, a population-based, case-control study of African-American and white women. Immunohistochemical markers were used to subtype 1,424 cases of invasive and in situ breast cancer, and case subtypes were compared to 2,022 controls. Luminal A, the most common subtype, exhibited risk factors typically reported for breast cancer in previous studies, including inverse associations for increased parity and younger age at first full-term pregnancy. Basal-like cases exhibited several associations that were opposite to those observed for luminal A, including increased risk for parity and younger age at first term full-term pregnancy. Longer duration breastfeeding, increasing number of children breastfed, and increasing number of months breastfeeding per child were each associated with reduced risk of basal-like breast cancer, but not luminal A. Women with multiple live births who did not breastfeed and women who used medications to suppress lactation were at increased risk of basal-like, but not luminal A, breast cancer. Elevated waist-hip ratio was associated with increased risk of luminal A in postmenopausal women, and increased risk of basal-like breast cancer in pre- and postmenopausal women. The prevalence of basal-like breast cancer was highest among premenopausal African-American women, who also showed the highest prevalence of basal-like risk factors. Among younger African-American women, we estimate that up to 68% of basal-like breast cancer could be prevented by promoting breastfeeding and reducing abdominal adiposity.
Breast Cancer Res Treat 2008 May
PMID:Epidemiology of basal-like breast cancer. 1757 64

We develop a new technique to analyse microarray data which uses a combination of principal components analysis and consensus ensemble k-clustering to find robust clusters and gene markers in the data. We apply our method to a public microarray breast cancer dataset which has expression levels of genes in normal samples as well as in three pathological stages of disease; namely, atypical ductal hyperplasia or ADH, ductal carcinoma in situ or DCIS and invasive ductal carcinoma or IDC. Our method averages over clustering techniques and data perturbation to find stable, robust clusters and gene markers. We identify the clusters and their pathways with distinct subtypes of breast cancer (Luminal,Basal and Her2+). We confirm that the cancer phenotype develops early (in early hyperplasia or ADH stage) and find from our analysis that each subtype progresses from ADH to DCIS to IDC along its own specific pathway, as if each was a distinct disease.
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PMID:Analysis of breast cancer progression using principal component analysis and clustering. 1791 45

Breast carcinomas are characterized by DNA copy number alterations (CNAs) with biological and clinical significance. This explorative study integrated CNA, expression, and germline genotype data of 112 early-stage breast cancer patients. Recurrent CNAs differed substantially between tumor subtypes classified according to expression pattern. Deletion of 16q was overrepresented in Luminal A, and a predictor of good prognosis, both overall and for the nonluminal A subgroups. The deleted region most significantly associated with survival mapped to 16q22.2, harboring the genes TXNL4B and DXH38, whose expression was strongly correlated with the deletion. The area most frequently deleted resided on 16q23.1, 3.5 MB downstream of the area most significantly associated with survival, and included the tumor suppressor gene ADAMTS18 and the cell recognition gene CNTNAP4. Whole-genome association analysis identified germline single nucleotide polymorphisms (SNPs) and their corresponding haplotypes, residing on several different chromosomes, to be associated with deletion of 16q. The genes where these SNPs reside encode proteins involved in the extracellular matrix (CHST3 and SPOCK2), in regulation of the cell cycle (JMY, PTPRN2, and Cwf19L2) and chromosome stability (KPNB1).
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PMID:Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients. 1839 21


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