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

Few would argue that there is not substantial room for an improvement in breast cancer practice. It has to be borne in mind that the United Kingdom experience in the 1980s was a 50:50 survival to death ratio in the 10 years after diagnosis. Preliminary analysis of the effects of mammographic screening suggests that there will be a real but small fall in overall mortality. Existing practice involves three stages: first, the 'earliest' detection of a lump by palpation or imaging; second, diagnosis by histopathology; and third, treatment by surgery, etc. Evidence is given that the limited success of existing practice could be due, in part, to a failure to recognize the precancerous state of the mammary tissue as a whole in cancer cases; and a failure to exploit this state for earlier diagnosis. In support of these contentions, comparative data from the microscopy of cancer-associated breasts and age-matched normal breast are given. There is a gross excess of focal hyperplasia in premenopausal cancer-associated breast tissue. Further, epidemiological data are consistent in that the tissue is subject to a sixfold increase in the risk of further primary carcinogenesis. A method is presented for detecting the cancer-associated breast. It exploits the breast menstrual cycle, a subject which is reviewed in extenso. Physiologically the premenopausal mammary tissue goes into a monthly pregnancy rehearsal with glandular proliferation and increased blood supply. The latter effects a luteal heat cycle, which can be measured readily by an electronic thermometric bra as increased breast surface temperature (1 degree C). Data are presented in terms of 50 normal breasts and 41 cancer-associated breasts studied daily (with progesterone assays) for one menstrual cycle. The cancer-associated breasts exhibit an absent or altered response to endogenous progesterone during the luteal phase of the menstrual cycle. The abnormality in the luteal heat cycle is maximal during the few days just after ovulation. Our data indicate that a 1-h clinical test at this time achieves a sensitivity of 71% and a specificity of 80% for "clinically normal' yet cancer-associated breast tissue. Such patients would be candidates for increased surveillance and chemoprevention.
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PMID:Sir James Young Simpson Memorial Lecture 1995. Breast cancer prevention: a pathologist's approach. 899 20

Breast cancer antigens RAK-p120, -p42, -p25 were detected in 100% of breast cancer cases tested (71 cases). Only 10% of adjacent tissue cases tested positive for all three cancer antigens, and 17.5% of the cases tested positive for two antigens only. Eighty-five percent of histologically normal breast tissue samples, isolated either from breast cancer patients or patients with advanced fibrocystic disease, tested RAK-negative, with the exception of low expression of p25, observed in some patients. Polymerase chain reaction (PCR) with HIV-1 gp 41-derived primers revealed cancer-associated DNA fragments of similar size (140 bp) as in HIV-1 genome. Fifty-four percent of cancer adjacent tissues, and 50% of malignancy-free breast tissue samples, tested PCR-negative. It is suggested that genetic predisposition to cancer may be associated with the presence of RAK genes, while expression of RAK antigens marks an already ongoing process of malignant changes.
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PMID:New protein and PCR markers RAK for diagnosis, prognosis and surgery guidance for breast cancer. 902 74

Carbohydrate antigens have been identified as significant antigens in many human tumors either by analyzing antibodies in patients' sera or by using monoclonal antibodies of either mouse or human origin. Three carbohydrate epitopes present on cancer-associated mucins [sialyl-Lewis A (SLA), sialyl-Lewis X (SLX), and sialyl-Tn (STn)] may have functional significance in metastasis. Subsequently, these antigens are considered as targets for active specific immunotherapy. Carbohydrates, as T-cell-independent antigens, often elicit diminished immune responses. To overcome this drawback, carbohydrates are typically coupled to protein carriers to elicit immunoglobulin G (IgG) responses as opposed to low-affinity IgM responses, which often times accompanies carbohydrate-based immunizations. In addition, some complex carbohydrates are difficult to synthesize. This latter aspect is further magnified if one considers that clustering of epitopes on neoglycoproteins must be emulated in the synthesis process, leading to multiple presentation or tandem repeats of the synthetic carbohydrate immunogen. Here, we examine the hypothesis that peptides that mimic carbohydrates might be developed to induce immune responses that target and mediate the killing of tumor cells, particularly breast cancer cells in an adjuvant-type setting. We have found that carbohydrate-mimicking peptides retain carbohydrate-like conformations, inducing anti-carbohydrate immune responses against breast tumor cells and mediating their killing by a complement-dependent mechanism.
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PMID:Peptide mimicry of adenocarcinoma-associated carbohydrate antigens. 908 21

In view of the methodological problems of epidemiological studies on associations between residential and occupational exposures to 50/60-Hz magnetic fields (MF) and increased incidence of cancers, laboratory studies are necessary to determine if 50/60-Hz MF can affect cancer development or growth. Recently, it was reported that alternating (50-Hz) MF of low flux density (100 microT) increase tumor growth and progression in a model of breast cancer in female rats in which mammary tumors were induced by the chemical carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). The objective of the present study was to determine if a replicate experiment carried out in the same laboratory under the same experimental conditions yields a significant increase in tumor development and growth of similar magnitude. For the MF experiment, a group of 99 female Sprague-Dawley rats was exposed to a homogeneous horizontally polarized MF for 24 h/d (minus time for weighing, tumor palpation, cage cleaning, cage rotation), 7 d/wk; another group of 99 rats was sham exposed. DMBA was administered intragastrically at a dose of 5 mg/rat at the first day of exposure and at weekly intervals thereafter up to a total dose of 20 mg/rat. Duration of MF or sham exposure was 91 d. In both MF-exposed and sham-exposed rats, the first tumors could be recorded 6 wk after the initial DMBA application. At 9 wk after DMBA application, the group of MF-exposed rats exhibited significantly more animals with tumors than the sham-exposed group. This significant difference in the rate of tumor development was observed throughout the subsequent period of exposure. After autopsy, the incidence of macroscopically visible mammary tumors was 62% in controls, but 83% in MF-exposed rats, with the 35% difference between groups being statistically significant. Data substantiate that long-term exposure of DMBA-treated female Sprague-Dawley rats in an alternating MF of low flux density promotes the development and growth of mammary tumors, thus indicating that MF exposure exerts tumor-promoting and/or copromoting effects. Furthermore, the data show that the effects of MF exposure in the DMBA breast cancer model are reproducible if the same experiment is repeated in the same laboratory.
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PMID:Acceleration of mammary tumorigenesis by exposure of 7,12-dimethylbenz[a]anthracene-treated female rats in a 50-Hz, 100-microT magnetic field: replication study. 951 42

The cellular protooncogene MYC encodes a nuclear transcription factor that is involved in regulating important cellular functions, including cell cycle progression, differentiation, and apoptosis. Dysregulated MYC expression appears critical to the development of various types of malignancies, and thus factors involved in regulating MYC expression may also play a key role in the pathogenesis of certain cancers. We have cloned one such MYC regulatory factor, termed CTCF, which is a highly evolutionarily conserved-11-zinc finger transcriptional factor possessing multiple DNA sequence specificity. CTCF binds to a number of important regulatory regions within the 5' noncoding sequence of the human MYC oncogene, and it can regulate its transcription in several experimental systems. CTCF mRNA is expressed in cells of multiple different lineages. Enforced ectopic expression of CTCF inhibits cell growth in culture. Southern blot analyses and fluorescence in situ hybridization (FISH) with normal human metaphase chromosomes showed that the human CTCF is a single-copy gene situated at chromosome locus 16q22. Cytogenetic studies have pointed out that chromosome abnormalities (deletions) at this locus frequently occur in many different human malignancies, suggesting the presence of one or more tumor suppressor genes in the region. To narrow down their localization, several loss of heterozygosity (LOH) studies of chromosome arm 16q in sporadic breast and prostate cancers have been carried out to define the most recurrent and smallest region(s) of overlap (SRO) for commonly deleted chromosome arm 16q material. For CTCF to be considered as a candidate tumor suppressor gene associated with tumorigenesis, it should localize within one of the SROs at 16q. Fine-mapping of CTCF has enabled us to assign the CTCF gene to about a 2 centiMorgan (cM) interval of 16q22.1 between the somatic cell hybrid breakpoints CY130(D) and CY4, which is between markers D16S186 (16AC16-101) and D16S496 (AFM214zg5). This relatively small region, containing the CTCF gene, overlaps the most frequently observed SROs for common chromosomal deletions found in sporadic breast and prostate tumors. In one of four analyzed paired DNA samples from primary breast cancer patients, we have detected a tumor-specific rearrangement of CTCF exons encoding the 11-zinc-finger domain. Therefore, taken together with other CTCF properties, localization of CTCF to a narrow cancer-associated chromosome region suggests that CTCF is a novel candidate tumor suppressor gene at 16q22.1.
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PMID:A widely expressed transcription factor with multiple DNA sequence specificity, CTCF, is localized at chromosome segment 16q22.1 within one of the smallest regions of overlap for common deletions in breast and prostate cancers. 959 31

Microsatellite instability (MI+) is associated with defects in mismatch repair, resulting in a 'mutator' phenotype and the development and progression of cancer. MI+ has been documented in invasive breast carcinomas. This study was undertaken to determine whether MI+ is found in the early non-invasive form of breast cancer, ductal carcinoma in situ (DCIS). We examined microdissected ducts from 23 cases of DCIS with 11 markers comprising mono-, di-, and trinucleotide repeats from six chromosomal regions. Five tumours (22 per cent) displayed MI+ at two or more loci, in all ducts examined. A further seven (30 per cent) tumours showed alterations at a single locus (the DM-1 trinucleotide), and for two of these, heterogeneity between ducts was observed. Alterations at microsatellite repeat motifs in the coding regions of four cancer-associated genes (TGF beta RII, IGFIIR, BAX, and E2F-4) were not observed. Immunohistochemistry revealed that there was no loss of reactivity for the mismatch repair proteins, MLH1, MSH2, and PMS2, in the DCIS cases. In general, MI+ tumours and those with alterations at the DM-1 microsatellite were predominantly of higher nuclear grade and expressing c-erbB-2, suggesting that aberrations in DNA repair functions may lead to the acquisition of a more aggressive phenotype in breast cancer.
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PMID:Microsatellite instability in ductal carcinoma in situ of the breast. 971 55

Three founder mutations in the cancer-associated genes BRCA1 and BRCA2 occur frequently enough among Ashkenazi Jews to warrant consideration of genetic testing outside the setting of high-risk families with multiple cases of breast or ovarian cancer. We estimated the prevalence of these founder mutations in BRCA1 and BRCA2 in the general population of Ashkenazi Jews according to age at testing, personal cancer history, and family cancer history. We compared the results of anonymous genetic testing of blood samples obtained in a survey of >5,000 Jewish participants from the Washington, DC, area with personal and family cancer histories obtained from questionnaires completed by the participants. In all subgroups defined by age and cancer history, fewer mutations were found in this community sample than in clinical series studied to date. For example, 11 (10%) of 109 Jewish women who had been given a diagnosis of breast cancer in their forties carried one of the mutations. The most important predictor of mutation status was a previous diagnosis of breast or ovarian cancer. In men and in women never given a diagnosis of cancer, family history of breast cancer before age 50 years was the strongest predictor. As interest in genetic testing for BRCA1 and BRCA2 in the Jewish community broadens, community-based estimates such as these help guide those seeking and those offering such testing. Even with accurate estimates of the likelihood of carrying a mutation and the likelihood of developing cancer if a mutation is detected, the most vexing clinical problems remain.
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PMID:The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. 1057 33

A total of 18 families with multiple cases of breast cancer were identified from southern Taiwan, and 5 of these families were found to carry cancer-associated germline mutations in the BRCA1 and BRCA2 genes. One novel cryptic splicing mutation of the BRCA1 gene, found in two unrelated families, was shown to be a deletion of 10 bp near the branch site in intron 7. This mutation causes an insertion of 59 nucleotides derived from intron 7 and results in a frameshift, leading to premature translational termination of BRCA1 mRNA in exon 8. Deletions of 2670delC, 3073delT and 6696-7delTC in the BRCA2 gene were found in three other breast cancer families. All three deletions are predicted to generate frameshifts and to result in the premature termination of BRCA2 protein translation. Several genetic polymorphisms in both BRCA1 and BRCA2 genes were also detected in this investigation.
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PMID:Molecular characterization of germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in Taiwan. 1032 42

This study was designed to evaluate new bone resorption and tumour markers as possible alternatives to serial plain radiographs for the assessment of response to treatment. Thirty-seven patients with newly diagnosed bone metastases from breast cancer, randomized to receive oral pamidronate or placebo tablets in addition to anticancer treatment within the context of a multicentre EORTC trial, who were both assessable for radiographic response in bone and had serum and urine samples collected for more than 1 month were studied. The markers of bone metabolism measured included urinary calcium (uCa), hydroxyproline (hyp), the N-telopeptide cross-links of type I collagen (NTx) and total alkaline phosphatase. The tumour markers measured were CA15-3 and cancer-associated serum antigen (CASA). Before treatment, levels of Ntx, uCa and Hyp were elevated in 41%, 24% and 28% respectively, and CA15-3 and CASA increased in 69% and 50%. For assessment of response and identification of progression, Ntx was the most useful bone marker. All markers behaved similarly in no change (NC) and partial response (PR) patients. There was a significant difference (P < or = 0.05) in Ntx levels (compared to baseline) at 1 and 4 months and in CA15-3/CASA at 4 months between patients with PR or NC and those with progressive disease (PD), and at 4 months between those with time to progression (TP) > 7 and those with TP < or = 7 months. The diagnostic efficiency (DE) for prediction of PD following a > 50% increase in Ntx or CA15-3 was 78% and 62% respectively. An algorithm to predict response to therapy has been developed for future prospective evaluation.
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PMID:Assessment of bone response to systemic therapy in an EORTC trial: preliminary experience with the use of collagen cross-link excretion. European Organization for Research and Treatment of Cancer. 1039

Epidemiology suggests a possible relationship between exposure to power frequency magnetic fields (EMF) and breast cancer. One mechanism through which EMF could stimulate breast cancer induction is via altered expression of oncogenes and/or tumor suppressor genes that regulate normal and neoplastic growth. To evaluate the hypothesis that EMF action in the breast is mediated by alterations in gene expression, transcript levels of c-myc and a battery of other cancer-associated genes were quantitated in human breast epithelial cells exposed to pure, linearly polarized 60 Hz EMF with low harmonic distortion. HBL-100 cells and normal (non-transformed) human mammary epithelial cells were exposed to EMF flux densities of 0.1, 1.0 and 10.0 Gauss (G) for periods ranging from 20 min to 24 h; concurrent sham controls were exposed to ambient fields (<0.001 G) only. Gene expression was quantitated using ribonuclease protection assays. EMF exposure had no statistically significant effect on basal levels of c-myc transcripts in either human breast cell model, and had no effect on alterations in c-myc expression induced by 12-O-tetradecanoylphorbol-13-acetate. Transcript levels of c-erbB-2, p53, p21, GADD45, bax, bcl-x, mcl-1, and c-fos were also unaffected by EMF exposure. These results suggest that EMF is unlikely to influence breast cancer induction through a mechanism involving altered expression of these genes.
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PMID:Gene expression in human breast epithelial cells exposed to 60 Hz magnetic fields. 1042 19


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