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

The development of familial and sporadic breast cancer is based on genetic alterations of tumour-suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation. To investigate LOH of BRCA1 (17q21) and BRCA2 (13-q12-13) in sporadic breast cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for detection of microsatellite polymorphisms was applied. A total of 137 breast cancer and 15 benign breast specimens with matched normal tissue were examined. Fluorescent-labelled PCR products were analysed in an automated DNA sequencer (ALFTM Pharmacia). Losses at both loci were correlated with different histological types, age, tumour size, lymph node status, grading and steroid hormone receptor expression, [SHR: oestrogen receptor (ER), progesterone receptor (PgR)]. For BRCA1 (D17S855, THRA1, D17S579) losses could be detected in invasive ductal carcinoma (IDC; n = 108) in 32-38%, invasive lobular carcinoma (ILC; n = 19) in 21-42% depending on the marker applied, but not in benign breast tumours (n = 15). Losses of BRCA1 markers correlated with larger tumour size, higher grade, and PgR expression. For BRCA2 (D13S260, D13S267, D13S171) losses could be detected in 108 IDCs in 30-38%, in 19 ILCs in 17-39% depending on the marker applied, but not in benign breast tumours. Losses of BRCA2 markers correlated only with higher grade. Microsatellite analyses combined with detection of fluorescent-labelled PCR products by an automated laser DNA sequencer can be used for routine determination of LOH. In sporadic breast cancer, LOH of BRCA1 of BRCA2 does not add decisive prognostic value as stated for familial breast cancer.
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PMID:Clinical impact of detection of loss of heterozygosity of BRCA1 and BRCA2 markers in sporadic breast cancer. 863 Feb 82

Conflicting data suggest that TGF-beta1 can either inhibit or promote the progression of breast cancer. To determine the biological role of TGF beta1 in mammary carcinoma, in this study we examined the gene structure, expression and localization of TGF-beta1 using paraffin-embedded samples from 32 (27 IDC, 1 ILC, 1 DCIS, 1 ADH) breast lesions. Gene mutations in the region coding for the active protein were investigated by PCR-SSCP of exons 5, 6, and 7. mRNA -TGF-beta1 expression and distribution was examined by NISH using cDNA probes generated by RT-PCR and immunohistochemistry. We detected two mutations in exon 6 TGF-beta1 from IDC; and TGF beta1 mRNA and proteins in 28 (87%) of the tumors. Invasive breast carcinomas had more intense TGF-beta1 activity than CIS and than normal tissue adjacent to tumor. TGF beta1 mRNA and proteins were higher at the edge of the tumor than in the center and were also higher in less differentiated breast neoplasms. TGF-beta1 mRNA transcription and protein levels did not correlate either with TGF-beta1 exon 6 mutation or type and grade of differentiation of breast tumors. These observations suggest that TGF beta1 mutations in breast neoplasms might cause loss or inactivation of the growth inhibitory effects of TGF-beta1. They also support the proposed role of TGF-beta1 in the pathogenesis of breast cancer.
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PMID:Molecular genetic analysis of TGF beta1 in breast cancer. 914 62

Invasive breast carcinomas are characterized by a complex pattern of chromosomal alterations. We applied comparative genomic hybridization (CGH) to analyze 105 primary breast carcinomas using histograms to indicate the incidence of DNA imbalances of tumor subgroups and difference histograms to compare invasive ductal carcinomas (IDC) with lobular carcinomas (ILC), well and poorly differentiated carcinomas (G1/G3) and estrogen receptor-positive and -negative tumors (ER(+)/ER(-)). Only single imbalances showed a higher incidence in ILC compared with IDC, i.e., gains on chromosomes 4 and 5q13-q23 as well as deletions on chromosomes 6q, 11q14-qter, 12p12-pter, 16q, 17p, 18q, 19, and 22q. Of these, particularly gains of 4 and losses at 16q21-q23, and 18q12-q21 were statistically significant. For most loci, IDC showed more alterations providing a genetic correlate to the fact that ductal carcinoma overall is associated with a worse prognosis than ILC. Of these, many imbalances showing statistical significance were also observed in G3 and ER(-) tumors, i.e., deletions at 2q35-q37, 3p12-p14, 4p15-p16, 5q, 7p15, 8p22-p23, 10q, 11p, 14q21-q31, 15q, and gains at 2p, 3q21-qter, 6p, 8q21-qter, 10p, 18p11-q11, and 20q, suggesting that they contribute to a more aggressive tumor phenotype. By contrast, gains on chromosome 5q13-q23 as well as deletions at 6q, 16q and 22q were more prevalent in G1 and ER(+) tumors. The ratio profiles of all cases as well as histograms are accessible at our CGH online tumor database at http://amba.charite.de/cgh. Our results highlight distinct chromosomal subregions for cancer-associated genes. In addition, these imbalances may serve as markers for a genetic classification of invasive breast cancer.
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PMID:Patterns of chromosomal imbalances in invasive breast cancer. 1086 9

During 1986-1987, 192 women aged 26-86 with invasive breast cancer were treated with radiotherapy, hormonotherapy, and chemotherapy and then underwent modified radical mastectomy or wide local excision at Luis Castelazo Ayala Hospital of Obstetrics and Gynecology of the Mexican Social Security Institute in Mexico City. At diagnosis, metastatic bone surveys and bone scans showed that no one had distant metastasis. The physicians used incisional biopsy to determine the type of breast carcinoma (infiltrating ductal carcinoma [IDC] and infiltrating lobular carcinoma [ILC]). The researchers aimed to identify prognostic factors in primary breast cancer. 156 patients (81.3%) and 36 patients (18.7%) had IDC and ILC, respectively. Among women with IDC, axillary nodes were involved in 23.5% of premenopausal women and in 23% of postmenopausal women. 83.8% of all patients with IDC and 52.3% of IDC patients aged at least 50 had clinical stage III disease. Among women with ILC, axillary nodes were involved in 19.4% of premenopausal women and in 19.4% of postmenopausal women. 70% of all patients with ILC and 84.6% of ILC patients aged at least 50 had clinical stage III disease. All the patients had advanced breast cancer (i.e., clinical stage II and III). Some tumors were only estrogen receptor types, while others were only progesterone receptor types. Some tumors were even both receptor types, while another category had neither steroid hormone receptor. Survival rates for metastatic and non-metastatic breast cancer was greater among postmenopausal women than premenopausal women (32.7% vs. 14.8% and 21.8% vs. 12.8% for ICD and 19.4% vs. 8.4% and 30.5% vs. 13.9% for ILC, respectively). These findings suggest that axillary node status, status of estrogen and progesterone receptors, and menstrual status were important prognostic factors of breast cancer.
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PMID:Infiltrating ductal / lobular carcinoma: an evaluation of prognostic factors in primary breast cancer. 1232 22

The aim of this study was to determine whether the metastatic potential of breast cancer could be related to phenotypic characteristics of the tumour. Therefore, we compared the metastatic patterns of invasive lobular (ILC) and ductal (IDC) carcinomas. In ILC, we also analysed this pattern according to the histological subtype of the primary and the E-cadherin (EC) expression level. Metastatic ILC cases (n=96) were retrospectively analysed and classified into classical, alveolar, solid, tubulo-lobular, signet ring cells or pleomorphic subtypes. Anatomical distribution of metastases was detailed for every patient and compared with that registered for IDC (n=2749). Immunostaining of EC (HECD1 antibody) was performed in 82 cases. Histologically, 78 of the 96 cases (81%) corresponded to classical ILC. The pleomorphic subtype was observed in 14 cases (15%), a rate that was higher than that expected. Others corresponded to alveolar (2 cases), signet ring cell (1 case) and solid (1 case) subtypes. EC was undetectable in 72/82 cases (88%). The rate of multiple metastases was higher in ILC (25.0%) than in IDC (15.8%) (P=0.016). Metastases were found more frequently in ILC than in IDC in the bone (P=0.02) and/or in various other sites (peritoneum, ovary, digestive tract, skin em leader ) (P<0.001). In ILC, no significant link was found between the localisation(s) of metastases, the histological subtype and the EC status in the primary. In conclusion, in breast carcinomas, the frequency of multiple metastasis was found to be higher in ILC than IDC. This fact may be related to the phenotypic trait of discohesive small cells which characterises ILC. EC loss, observed in most cases of ILC, may result in alterations in cell-cell adhesion and a preferential growth at metastatic sites. A high rate of pleomorphic tumours was observed in the group of metastatic ILC, but the pattern of metastatic site(s) was not related to the histological subtype of the primary.
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PMID:Wide metastatic spreading in infiltrating lobular carcinoma of the breast. 1474 50

Altogether 295 consecutive pure lobular invasive breast cancers diagnosed between 1990 and 1999 in the area of Tampere University Hospital were compared to 295 ductal invasive breast cancers. Biological factors, DFS, OS, recurrence types, survival after recurrence and other primary cancers were analyzed. ILC tumors were more often hormone receptor-positive, slowly proliferative and Erbb-2-negative. During the mean follow-up time of 5.1 years 76 recurrences in both groups were discovered. During the whole follow-up time there was more metastation to gynecological organs and GI tract in the ILC group. Bilateral breast cancers did not differ between the groups. DFS and OS were the same between the groups despite the fact that ILC patients received statistically significantly less adjuvant treatment. In conclusion, since ILC cancers are more often hormone receptor-positive, there is a good option to adjuvant endocrine therapy with present and future preparations, this possibly leading to improvement in OS.
Breast Cancer Res Treat 2004 May
PMID:A comparison of the biological and clinical features of invasive lobular and ductal carcinomas of the breast. 1503 95

In Japan, fine needle aspiration biopsy (FNA) of the breast has long been recognized as a useful diagnostic tool, and has been used in many institutions because it provides a rapid, accurate and cost-effective evaluation. However, the use of core needle biopsy (CNB) is increasing, and vacuum assisted biopsy devices have been developed to produce larger specimens for analysis. CNB is useful because the frequency of inadequate specimens is lower than in FNA, and it requires a less invasive procedure than open biopsy. CNB is also more widely used, compared to FNA, because it can provide a more definitive diagnosis of borderline lesions and can be used to distinguish between IDC and ILC. Therefore, the use of CNB with mammographic or ultrasonographic guidance is especially high for non-palpable tumors. FNA is a rapid and non-invasive procedure that is useful for mass lesions. The accuracy of FNA for non-palpable lesions is relatively low, and depends upon the skill of the aspirators, cytoscreeners and cytopathologists involved in the procedure. However, FNA for palpable masses, coupled with a physical and mammographic examination (the so-called triple test) is highly accurate for diagnosis of breast cancer when all three modalities indicate malignancy, and for a benign lesion when all three are negative.
Breast Cancer 2004
PMID:Core needle biopsy (CNB) as a diagnostic method for breast lesions: comparison with fine needle aspiration cytology (FNA). 1560 88

E-cadherin (E-CD) is an epithelial-specific cell adhesion molecule, whose expression is lost in invasive lobular (ILC) but not in invasive ductal carcinoma (IDC) of the breast. This cell adhesion system can be disrupted by tyrosine kinase c-erbB-2/HER-2/neu. We examined 106 cases of high-grade invasive breast cancer, including 91 IDCs, 12 ILCs and 3 pleomorphic lobular carcinomas (PLCs). We determined Nottingham histological grade and performed immunohistochemistry for estrogen and progesterone receptors (ER/PR), Ki-67, E-CD and c-erbB-2/HER-2/neu with subsequent fluorescence in situ hybridization. Amplification of c-erbB-2/HER-2/neu gene was observed in 55/91 (60.4%) of IDCs, 3/12 (25%) of ILCs and 1/3 (33.3%) of PLCs, and associated with positive axillary lymph nodes. E-CD expression was lost in 14/91 (15.4%) of IDCs, 10/12 (83.3%) of ILCs and 2/3 (66.7%) of PLCs. The loss of E-CD immunoreactivity in IDCs appeared to be associated with c-erbB-2/HER-2/neu gene amplification, negative ER/PR status and positive lymph nodes, whereas E-CD-positive ILCs tended to be HER-2/neu-positive. The biological significance of E-CD expression seems to be different in high-grade IDC and ILC. Oncogenic pathway mediated by c-erbB-2/HER-2/neu may affect the E-CD expression in most invasive ductal breast carcinomas in vivo.
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PMID:Expression of E-cadherin and c-erbB-2/HER-2/neu oncoprotein in high-grade breast cancer. 1782 36

The aim of the present study was to evaluate the effectiveness of fluorescence in situ hybridisation (FISH), as a screening test, in moderately- (G2) or poorly- (G3) differentiated breast cancers of the ductal (IDC) and lobular (ILC) histotypes and distant metastases. HER2 FISH was performed on 486 G2 and 477 G3 both of IDC and ILC histotypes and in 241 metastases. A significant difference in the HER2 amplification was observed between G2 (14.8%) and G3 (31.9%), with no difference according to the histotype. However, the rate of amplification increased to 36% in the G2/hormone receptor-negative cases as compared to 10.6% in the G2/receptor-positive cases (p<0.0001). HER2 was amplified in 17% of metastases with some differences depending on the location. These data suggest that the HER2 FISH analysis may be an effective screening test in breast cancer metastases and G3 tumors, irrespective of the hormone receptor status or presence of lymphovascular invasion.
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PMID:Fluorescent in situ hybridization as a screening test for HER2 amplification in G2 and G3 breast cancers of lobular and ductal histotype and metastases. 1842 87

The oestrogen receptor-alpha (ER alpha) plays a key role in breast development and tumorigenesis and inhibiting its activity remains a prime strategy in the treatment of ER alpha-positive breast cancers. Thus, elucidation of the molecular mechanisms responsible for regulating ER alpha activity may facilitate the design of new, more effective breast cancer therapies. The MI-ER1 alpha is a novel transcriptional repressor that contains an LXXLL motif for interaction with nuclear hormone receptors. We investigated the ability of MI-ER1 alpha to bind to ER alpha in HEK293 and MCF-7 breast carcinoma cells, using co-immunoprecipitation assays. In both cell lines, MI-ER1 alpha interacted with ER alpha in the presence and absence of oestrogen, but the interaction was stronger in the absence of ligand. Functional analysis revealed that overexpression of MI-ER1 alpha in T47D breast carcinoma cells results in inhibition of oestrogen-stimulated anchorage-independent growth, suggesting that MI-ER1 alpha may play a role in regulating breast carcinoma cell proliferation in vivo. To explore this further, we performed an immunohistochemical analysis of normal breast tissue and breast carcinoma; a total of 110 cases were examined in whole tissue sections and 771 cases were analysed in tissue microarrays. No consistent difference in the MI-ER1 alpha expression level between normal breast tissue and breast carcinoma was discernible. However, there was a dramatic shift in the subcellular localisation: nuclear MI-ER1 alpha was detectable in 75% of normal breast samples and in 77% of hyperplasia, but in breast carcinoma, only 51% of DCIS, 25% of ILC and 4% of IDC contained nuclear staining. This shift from nuclear to cytoplasmic localisation of MI-ER1 alpha during breast cancer progression suggests that loss of nuclear MI-ER1 alpha might contribute to the development of invasive breast carcinoma.
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PMID:Changes in subcellular localisation of MI-ER1 alpha, a novel oestrogen receptor-alpha interacting protein, is associated with breast cancer progression. 1866 73


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