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Query: UMLS:C0007124 (ductal carcinoma in situ)
 3,833 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Certain dietary retinoids and polyunsaturated fatty acids (PUFAs) consistently inhibit progression of mammary carcinogenesis both in animal studies and cell culture, but clinically, their effect is inconsistent. New evidence of synergistic interaction between the nuclear receptors for the two groups of nutritional agents suggests that appropriate selective ligands from each group might be combined in breast cancer chemoprevention studies. Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor that is activated by PUFAs, eicosanoids and antidiabetic agents such as troglitazone. Such activation can cause growth inhibition in human mammary cancer cells in culture and the effect is enhanced by ligands of retinoic acid receptor (RAR) and retinoid X receptor (RXR). In mouse mammary tissue in organ culture, an RXR-selective ligand has been shown to enhance the effect of troglitazone in suppressing carcinogen-induced pre-neoplastic changes. A PPAR/RXR heterodimer is involved in tumour growth inhibition and has been shown to bind directly to nuclear oestrogen response elements (ERE) independently of oestrogen receptor (ER) activity. A combination of an RXR-selective retinoid with either troglitazone or else a long-chain n-3 PUFA, is proposed for a short-term study in postmenopausal women after primary surgery for intraductal breast cancer. The resulting activation of PPAR/RXR expression may increase response to retinoid administration, especially in the presence of obesity and insulin resistance, because of the ability of PPAR gamma ligands to reduce insulin-like growth factor I (IGF-I) concentrations. Serial core biopsies of breast tissue over a short term are proposed to identify changes in phenotype, which may influence progression to invasiveness. In addition to cytomorphological criteria, expression of ER alpha and beta, RAR alpha and beta, and IGF-I receptor in the nucleus should be examined.
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PMID:Linkage between retinoid and fatty acid receptors: implications for breast cancer prevention. 1219 57

Ductal carcinoma in situ (DCIS) of the breast is a premalignant condition which accounts for approximately 20% of all new breast cancers and up to 40% of neoplastic lesions detected by mammographic screening. Since recurrence is common after DCIS treated with breast conservation surgery, there is a need to determine molecular factors that predict recurrence. In parallel with this and with the finding that oestrogen receptor (ER) positive breast cancer can be prevented with anti-oestrogens, there have been recent advances in the understanding of the molecular biology of DCIS. Receptor coexpression in DCIS has been determined largely by immunohistochemistry. Animal models have provided evidence for the signalling pathways involved in the regulation and dysregulation of proliferation and apoptosis in both normal breast and in situ cancer. ER-negative DCIS has been shown to be hormone-independent. Blockade of the pathways involved in cell proliferation in ER-negative DCIS is possible and will be necessary to prevent ER-negative breast cancers if the goal of breast cancer chemoprevention is to be realistically achieved.
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PMID:Molecular markers and therapeutic targets in ductal carcinoma in situ. 1224 92

The optimal management of ductal carcinoma in situ (DCIS) is controversial, due in part to our poor understanding of its natural history. We undertook to identify subgroups of DCIS based on the expression of biomarkers, which were related to the likelihood of clinical recurrence. Biomarker expression of a total of 95 DCIS lesions in a nested case-control study within a population-based cohort with up to 135 months follow-up data (median 101 months) was analysed using immunohistochemistry. ERBB2-positivity and bcl-2-, oestrogen receptor (ER)- and progesterone receptor (PR)-negativity were individually associated with the risk of clinical recurrence. The predictive value of these biomarkers was independent of cytonuclear grade. ERBB2, bcl-2, ER and PR expression were conserved in the recurrent lesions, including subsequent invasive cancers. p21-positive DCIS was also associated with clinical recurrence, independently of the associations with ERBB2/bcl-2/ER/PR expression. These data identify clinically and biologically relevant subcategories of DCIS lesions, an essential basis for improving management.
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PMID:Biological markers that predict clinical recurrence in ductal carcinoma in situ of the breast. 1262 41

Adjuvant antioestrogen therapy with tamoxifen is recommended for all women following breast-conserving surgery for ductal carcinoma in situ (DCIS) to reduce local recurrence, despite 50% of lesions being oestrogen receptor (OR) negative. We have investigated the response to hormone manipulation in DCIS by studying changes in epithelial proliferation and progesterone receptor (PR) expression as surrogate molecular markers of treatment effects in DCIS of known OR status. Women were identified who had undergone diagnostic core biopsy followed by surgery for DCIS 14-41 days later. Ki67 (a measure of epithelial cell proliferation) and PR expression were determined by immunohistochemistry on paired paraffin sections of the core biopsy and operative specimens for each patient, with OR and HER-2 measured on the operative specimen. Women were divided into three groups according to whether they had changed hormone therapy (stopped hormone replacement therapy (HRT), group 1), continued taking HRT (group 2) or were not taking HRT (group 3) between core biopsy and surgery. In OR-positive (but not in OR-negative) DCIS after oestrogen withdrawal (group 1), a fall in the mean cell proliferation (P&<0.01) was observed. A fall in PR expression between core biopsy and surgery was also seen in this group (P=0.02). No change in either mean cell proliferation or PR expression was seen in the other two groups in OR-positive or -negative DCIS. The fall in proliferation and PR expression occurred regardless of HER-2 status. In conclusion, a biological response to hormone manipulation is only seen in OR-positive DCIS tumours. Any clinical value of antioestrogen therapy is likely to be restricted to this group.
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PMID:Biological response to hormonal manipulation in oestrogen receptor positive ductal carcinoma in situ of the breast. 1286 17

To gain insights into the possible role of oestrogen receptor (ER) beta in breast carcinogenesis, immunohistochemical analysis of ER beta was performed on 512 breast specimens encompassing normal (n = 138), pure ductal carcinoma in situ (n = 16), invasive cancers (n = 319), lymph node metastases (n = 31), and recurrences (n = 8). Real-time polymerase chain reaction (PCR) was used to investigate the methylation status of the ER beta gene in the ER beta negative breast cancer cell lines SkBr3 and MDA-MB-435. A gradual reduction in, but not a complete loss of, ER beta expression was observed during the transition from normal and pre-invasive lesions to invasive cancers, where ER beta was lost in 21% of cases. This was more pronounced in invasive ductal than in lobular carcinomas, a significantly higher proportion of which were ER beta-positive (74% compared with 91%, respectively, p = 0.0004). Examination of paired primary cancers with their axillary lymph node metastases showed that if ER beta was present in the primary tumour, it persisted in the metastasis. Treatment of ER beta-negative cell lines with DNA methyl transferase inhibitors restored ER beta expression, providing experimental evidence that silencing of ER beta in breast carcinomas could be due to promoter hypermethylation. These results suggest that loss of ER beta expression is one of the hallmarks of breast carcinogenesis and that it may be a reversible process involving methylation.
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PMID:Reduced expression of oestrogen receptor beta in invasive breast cancer and its re-expression using DNA methyl transferase inhibitors in a cell line model. 1451 38

Ductal carcinoma in situ (DCIS) of the breast constitutes about 10% of all diagnosed breast cancers and, despite surgical removal, it may recur, either as DCIS or invasive breast cancer. Nuclear grade and growth pattern according to Andersen et al as well as surgical margins are factors that have been used to predict local recurrence, but ideally a set of tumour-specific factors should be identified and used as prognostic markers. Many cell cycle regulatory gene products have been shown to be involved in the formation of tumours and are either oncogenes or suppressor genes and involved in key processes in the transformation. We therefore characterised the cell cycle regulators cyclin E, cyclin D1, p27 and p16 in a material of DCIS cases arranged in a tissue microarray. With a manual tissue arrayer, 52% of the initial 177 DCIS samples were successfully targeted allowing immunohistochemical analyses of all four proteins in 92 cases of DCIS. As also observed in invasive breast cancer, there was a trend indicating that DCIS cases with high cyclin D1 were cyclin E low and oestrogen receptor-positive, whereas cyclin E high DCIS cases were cyclin D1 low and oestrogen receptor-negative. For the 64 patients that did not receive postoperative radiotherapy, there were 16 local recurrences (eight DCIS and eight invasive breast cancer) during a mean follow-up time of 63 months. Cyclin E, p27 or p16 were not associated with local recurrence, but interestingly cyclin D1 was significantly and inversely associated with local recurrence, both using univariate and multivariate analyses. In summary, using a tissue array approach we have shown that cyclin D1, besides growth pattern, is a prognostic marker for local recurrence in DCIS.
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PMID:Tissue microarray analyses of G1/S-regulatory proteins in ductal carcinoma in situ of the breast indicate that low cyclin D1 is associated with local recurrence. 1461 4

Heat shock protein 27 (hsp-27) is a regulator of oestrogen receptor (ER) expression and a modulator of intracellular homeostasis. In this laboratory, Shaaban et al demonstrated the importance of ER-alpha, together with Ki67, in enhancing the progression of benign breast lesions of defined morphological types. To better understand the mechanisms by which ER-alpha promotes breast neoplasia, this study was performed to test the hypothesis that the roles of ER-alpha and hsp-27 may be defined by their quantitative expression in proliferative breast lesions of varying histological risk. The expression of hsp-27 was identified using a specific monoclonal antibody and analysed to assess the proportion of positive epithelial cells using digitised morphometric image analysis. The expression of ER-alpha was analysed by immunohistochemistry and Western blotting in a variety of benign (HUMA121) and malignant mammary cell lines, including ER-alpha(+) (MCF7, ZR-75, T47D) and ER-alpha(-) (MDA-MB 231) breast cancer cell lines. The data confirm that, during progression from normal through proliferative breast lesions to in situ cancer, there was a significant increase in both the proportion and the optical density of the epithelial cells expressing hsp-27. The mean levels of expression ranged from 7.4% of the total number of epithelial cells in normal lobules to 25.17% of epithelial cells in hyperplasias of usual type (HUT) to 61.1% of epithelial cells in ductal carcinoma in situ (P<0.001). The study has confirmed the expression of hsp-27 to be closely associated with ER-alpha(+) expression, and that its regulated expression occurs early along the mammary oncogenic pathway, supporting the initial hypothesis. It is our proposal that the differential expression of hsp-27 modulates the phenotypic behaviour of morphologically benign epithelial cells and hence may be an important determinant in initiating, or promoting, a population of human mammary cancers.
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PMID:Increased risk of malignant progression in benign proliferating breast lesions defined by expression of heat shock protein 27. 1471 Feb 27

Cyclooxygenase type-2 (COX-2) is overexpressed in malignant tumours including breast cancers, though the mechanism of upregulation is unclear. This study aimed to determine COX-2 expression in ductal carcinoma in situ (DCIS) in comparison to invasive breast cancer (IBC) and normal breast, and also to investigate the relationship of COX-2 expression with HER-2 expression, oestrogen receptor (ER), tumour grade and cellular proliferation (Ki67) in DCIS. Cyclooxygenase type-2, HER-2, ER and Ki67 expression were determined by immunohistochemistry on paraffin tissue sections of DCIS (n=187), IBC (n=65) and normal breast reduction tissue (n=60). Cyclooxygenase type-2 expression in DCIS (67%, P<0.001) and IBC (63%, P<0.001) was significantly greater than in normal breast (23%). There was no difference in COX-2 expression level between DCIS and IBC (P=0.87) or between normal breast from reduction mammoplasty tissue and normal breast ducts around DCIS (22%, P=0.29). In DCIS, COX-2 expression was associated with higher cellular proliferation rates (P<0.0001), nuclear grade (P=0.003), with ER negativity (P=0.003) and with HER-2 positivity (P<0.0001). Cyclooxygenase type-2 expression is upregulated in in situ breast cancer and is associated with surrogate markers of an aggressive DCIS phenotype including nonoestrogen-regulated signalling pathways. Cyclooxygenase type-2 inhibition may potentially prevent the development of ER-positive and ER-negative breast cancers.
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PMID:COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ. 1473 88

The key to diagnosis for deformed or scaling nipple is cytology or histology. While scrape cytology and punch biopsy do not provide underlying breast tissue for histology wedge excision requires more time and resource. We present the technique of nipple core biopsy (NCB) in 40 patients with deformed or scaling nipple done as a part of triple assessment yielding both skin and breast tissue for histological examination. Histological diagnosis confirmed eczema in 24, Paget's disease of nipple in 9 and chronic inflammation in 2. Among 5 remaining patients with normal skin histology, underlying breast invasive ductal carcinoma was seen in 3, ductal carcinoma in situ (DCIS) in 1 and adenoma in 1. NCB identified 5(55%) significant breast pathologies in Paget's disease and detected a further 2 invasive cancers in the absence of a palpable mass. The technique also provides additional information in the form of oestrogen receptor, which can have direct impact on patient management.
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PMID:Nipple core biopsy for the deformed or scaling nipple. 1532 73

Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low- and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.
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PMID:Molecular evolution of breast cancer. 1564 Oct 21


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