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

Although there is no recommended screening for ovarian or endometrial cancers, the use of oral contraceptives is a primary prevention maneuver. The prevention of cervical cancer is accomplished best by Pap smear screening every 1 to 3 years. Clinical breast examination and mammography every 1 to 2 years after age 50 years are effective in reducing breast cancer mortality. Screening for BRCA1 and BRCA2 mutations is now available, but the role of these tests is still not clear; extensive patient counseling is required.
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PMID:Cancer prevention and screening in women. 901 27

To appreciate the involvement of known or potential susceptibility genes in sporadic breast tumors, we have searched for chromosomal deletions by studying loss of heterozygosity (LOH) at 43 microsatellite (CA)n markers from human chromosomes 10, 11 and 17, in 115 unselected consecutive samples of breast carcinoma with particular emphasis on specific regions. No site of consistent LOH was identified on chromosome 10. Five regions of LOH were contained within bands q22-24 of chromosome 11 for which nearly 50% of the tumors had LOH at at least one marker. This region is thus a major site of deletion in breast cancer and several tumor suppressor genes seem to be involved. One of them may be the ataxia telangiectasia (ATM) gene which is located in one of the affected regions. Five regions of LOH, one of which is within the BRCA1 gene area, were recognized along chromosome 17. LOH at three of these regions were found in highly proliferative tumors. When combined with a previous study of chromosome 13 with emphasis on BRCA2 and Rb1 genes, this work allowed to distinguish a total of 12 regions of LOH, variably affected in breast tumors and correlated with prognostic parameters.
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PMID:Loss of heterozygosity in human breast carcinomas in the ataxia telangiectasia, Cowden disease and BRCA1 gene regions. 901 20

The recent identification of genes that predispose their carriers to breast and ovarian cancer promises to shed light on the biology of cancer susceptibility. Individuals with mutations in the BRCA1 gene on chromosome 17 and the BRCA2 gene on chromosome 13 have four to eight times the risk of developing breast cancer as women in the general population. The many mutations that have been identified in both genes are predicted to produce a truncated, presumably nonfunctional, protein. Individuals of Ashkenazi Jewish decent have been found to carry specific BRCA1 and BRCA2 mutations. The sequences of BRCA1 and BRCA2 are not similar to any other previously cloned genes. Investigations are underway to elucidate the biological function of these genes. In the meantime, these genes offer the opportunity for members of high incidence cancer families to decide whether to undergo predisposition testing. There is a paucity of data to guide physicians in making follow-up recommendations to those who are found to be carrying a mutation. Thus, decisions about testing are personal and demand pretest education and counseling about the risks, benefits, and limitations. Further research into testing decisions and their outcome is greatly needed.
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PMID:Genetic susceptibility testing for breast and ovarian cancer: a progress report. 903 68

Epidemiologic data support the existence of two discrete manifestations of hereditary ovarian carcinoma: the breast and ovarian cancer syndrome and the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome. Genetic linkage analyses reveal that the majority of breast and ovarian cancer families are linked to the BRCA1 gene, while some cases of hereditary ovarian cancer are also apparent in breast cancer families linked to the BRCA2 gene. The majority of HNPCC families are linked to one of four genes encoding a family of DNA mismatch repair proteins. Molecular analyses demonstrate that genetic screening for germline transmission of a defective allele of one or another of these genes is now possible for high-risk individuals. The ethical, legal, and social implications of this type of analysis are multiple and complex, and genetic counseling requires a thorough understanding of these issues and a cautious approach to most effectively meet the special needs of this patient population. Increased medical surveillance and prophylactic oophorectomy are among the management options that may be appropriate for some genetically predisposed, asymptomatic women. Further research is needed regarding the most effective use of this genetic information in formulating counseling and clinical management strategies.
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PMID:Hereditary ovarian cancer: molecular genetics and clinical implications. 903 64

To estimate the proportion of breast cancer families due to BRCA1 or BRCA2, we performed mutation screening of the entire coding regions of both genes supplemented with linkage analysis of 31 families, 8 containing male breast cancers and 23 site-specific female breast cancer. A combination of protein-truncation test and SSCP or heteroduplex analyses was used for mutation screening complemented, where possible, by the analysis of expression level of BRCA1 and BRCA2 alleles. Six of the eight families with male breast cancer revealed frameshift mutations, two in BRCA1 and four in BRCA2. Although most families with female site-specific breast cancers were thought to be due to mutations in either BRCA1 or BRCA2, we identified only eight mutations in our series of 23 site-specific female breast cancer families (34%), four in BRCA1 and four in BRCA2. According to the posterior probabilities calculated for mutation-negative families, based on linkage data and mutation screening results, we would expect 8-10 site-specific female breast cancer families of our series to be due to neither BRCA1 nor BRCA2. Thus, our results suggest the existence of at least one more major breast cancer-susceptibility gene.
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PMID:Mutations in BRCA1 and BRCA2 in breast cancer families: are there more breast cancer-susceptibility genes? 1117 Sep 3

The mutations 185delAG, 188del11, and 5382insC in the BRCA1 gene and 6174delT in the BRCA2 gene were analyzed in 199 Ashkenazi and 44 non-Ashkenazi Jewish unrelated patients with breast and/or ovarian cancer. Of the Jewish Ashkenazi women with ovarian cancer, 62% (13/21) had one of the target mutations, as did 30% (13/43) of women with breast cancer alone diagnosed before the age 40 years and 10% (15/141) of those with breast cancer diagnosed after the age 40 years. Age at ovarian cancer diagnosis was not associated with carrier status. Of 99 Ashkenazi patients with no family history of breast and/or ovarian cancer, 10% carried one of the mutations; in two of them the mutation was proved to be paternally transmitted. One non-Ashkenazi Jewish ovarian cancer patient from Iraq carried the 185delAG mutation. Individual mutation frequencies among breast cancer Ashkenazi patients were 6.7% for 185delAG, 2.2% for 5382insC, and 4.5% for 6174delT, among ovarian cancer patients; 185delAG and 6174delT were about equally common (33% and 29%, respectively), but no ovarian cancer patient carried the 5382insC. More mutations responsible for inherited breast and ovarian cancer probably remain to be found in this population, since 79% of high-incidence breast cancer families and 35% of high-incidence breast/ovarian cancer families had none of the three known founder mutations.
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PMID:The founder mutations 185delAG and 5382insC in BRCA1 and 6174delT in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. 904 9

Women from families with multiple breast and/or ovarian cancers may be at increased risk to develop breast/ovarian cancer themselves. Due to personal experience with family members having these diseases they are anxious and ask for specific prophylactic measurements or treatment. The detection of two susceptibility genes, BRCA1 and BRCA2, has given insight into the genetic background of part of the familial breast/ovarian cancer syndromes. This has led to an increased demand in genetic counselling, testing, and early cancer detection programmes. Prospective data from early cancer detection programmes in this high risk population are yet not available. Based on data from epidemiological risk studies, breast and ovarian screening programmes and follow up data from breast cancer trials recommendations for an early cancer detection programme have been summarized. At the present these recommendations are tested in a prospective trial.
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PMID:Early cancer detection programmes for women at high risk for breast and ovarian cancer: a proposal of practical guidelines. 906 Dec 78

Most multiple case families of young onset breast cancer and ovarian cancer are thought to be due to highly penetrant mutations in the predisposing genes BRCA1 and BRCA2. However, these mutations are uncommon in the population and they probably account for only a few percent of all breast cancer incidence. A much larger fraction of breast cancer might, in principle, be due to common variants which confer more modest individual risks. There are several common polymorphisms in the BRCA1 gene which generate amino acid substitutions. We have examined the frequency of four of these polymorphisms: Gln356Arg, Pro871Leu, Glu1038Gly and Ser1613Gly in large series of breast and ovarian cancer cases and matched controls. Due to strong linkage disequilibrium, these four sites generate only three haplotypes with a frequency > 1.3%. The most common haplotypes, defined by the alleles Gln356Pro871Glu1038Ser1613 and Gln356Leu871Gly1038Gly1613, have frequencies of 0.57 and 0.32 respectively, and these frequencies do not differ significantly between patient and control groups. Thus the most common polymorphisms of the BRCA1 gene do not make a significant contribution to breast or ovarian cancer risk. However, our data suggest that the Arg356 allele may have a different genotype distribution in breast cancer patients from that in controls (Arg356 homozygotes are more frequent in the control groups, P = 0.01), indicating that it may be protective against breast cancer. If this finding can be confirmed, it may provide an insight into the structural features of the BRCA1 protein that are important for its function.
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PMID:Common BRCA1 variants and susceptibility to breast and ovarian cancer in the general population. 906 49

A proportion of human breast cancers result from an inherited predisposition to the disease. Mutations in the BRCA2 gene confer a high risk of breast cancer and are responsible for almost half of these cases. The recent cloning of the human BRCA2 gene has revealed that it encodes a large protein having little significant homology to known proteins. Here we describe the mouse Brca2 gene. The gene maps to mouse chromosome 5, consistent with its location on human chromosome 13q12. We have sequenced cDNA for the entire 3329 amino acid Brca2 protein and this has revealed that, like Brca1, Brca2 is relatively poorly conserved between humans and mice. Brca2 is transcribed in a diverse range of mouse tissues, and the pattern of expression is strikingly similar to that of Brca1. Taken together, our data highlight some intriguing similarities between two genes involved in inherited breast cancer susceptibility.
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PMID:Cloning, chromosomal mapping and expression pattern of the mouse Brca2 gene. 906 50

Between 5% and 10% of breast cancer cases result from an inherited predisposition. The majority of hereditary forms of breast and ovarian cancer can be accounted for by mutations in two recently identified genes, BRCA1 and BRCA2. Inactivating mutations have been found throughout both genes, and the majority are predicted to result in truncated proteins. Surprisingly, whereas germline mutations have been identified in a growing number of breast or breast and ovarian cancer families, few mutations have been reported in sporadic forms of breast or ovarian cancer. Alternative mechanisms of inactivation have been proposed, but there is currently no strong evidence that these genes are involved in sporadic forms of cancer. Recent studies suggest a role for BRCA1 in transcriptional regulation, as it possesses a conserved amino terminal RING finger domain and an acidic carboxyl domain. Although this role would be consistent with the reported localization of the BRCA1 protein to the nucleus, a cytoplasmic localization and a secretory role for BRCA1 has also been proposed. Current findings suggest that BRCA1 may play an as yet undefined protective role in cells, as it is strongly expressed in epithelial cells undergoing high levels of proliferation in association with differentiation.
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PMID:The BRCA1 and BRCA2 breast cancer genes. 909 Apr 99


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