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

Clinicians should recognize the genetic syndromes that predispose to the development of breast cancer so that patients may be afforded the opportunity to have genetic testing to assist them and their family members in making medical management decisions. Approximately 80%-90% of hereditary breast cancer cases are caused by mutations in the BRCA1 and BRCA2 genes. Other important clinical genetic predispositions include Cowden syndrome, Li-Fraumeni syndrome, Peutz-Jeghers syndrome, and ataxia-telangiectasia. The key to identifying women who are at risk for a hereditary breast cancer lies in obtaining an adequate, three-generation family history, including ethnic background. For unaffected women, breast cancer risks can be estimated using the quantitative models of Gail and Claus, but there are limitations to these models. Other quantitative models predict the likelihood that a patient is carrying a mutated gene. Genetic testing is available at selected laboratories for each of the hereditary syndromes described, and there are three possible outcomes to testing. These outcomes and their management implications are described in detail. Clinical management options for women at high risk for breast cancer include surveillance, chemoprevention, and prophylactic surgery. Application of these principles can reduce morbidity in women with genetic predispositions to breast cancer.
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PMID:Recognition and management of hereditary breast cancer syndromes. 1475 11

Cancer risk programs rely on accurately reported family history information. This study compares the accuracy with which cancer sites and ages at diagnosis are reported by Li-Fraumeni syndrome (LFS) and hereditary breast-ovarian cancer syndrome (HBOCS) families undergoing genetic testing. We analyzed the accuracy of 191 cancer diagnoses among first-degree (FDRs) and second-degree (SDRs) relatives reported by 32 LFS and 52 HBOCS participants in genetic testing programs. Cancer diagnoses of relatives were more accurately reported in the HBOCS cohort (78%) than in the LFS cohort (52%). Almost all breast cancer diagnoses were accurately reported, whereas 74% of ovarian cancer diagnoses and only 55% of other LFS-related cancers were accurately reported. Age at diagnosis was accurate within 5 years for 60% of LFS relatives and 53% of HBOCS relatives. Factors correlating with accurate reporting of cancer history included: being member of BRCA1 family, higher education level, female historian, degree of closeness to affected relative, and having fewer than 5 affected FDRs and SDRs. Relying on verbal histories would not have altered eligibility for genetic testing among HBOCS historians, but fewer than half of LFS historians provided information that would have led to TP53 testing. Our data suggest that it may not be necessary to confirm breast cancer diagnoses routinely; however, documentation of other cancer types remains important for appropriate risk assessment and follow-up.
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PMID:Accuracy of cancer family histories: comparison of two breast cancer syndromes. 1572 43

We screened the TP53 gene for mutational status in 40 breast tumor cases by polymerase chain reaction, single-strand conformational polymorphism, and gene sequencing. Many mutations of this gene have been described in specific databases. In our study, a new T-->C point mutation was identified in intron 6 at position 13989 in a grade III medullary ductal carcinoma. Other variations in intron 6 have been described in patients with Li-Fraumeni syndrome. One of these variations was reported to inhibit apoptosis and prolong cell survival, thereby increasing breast cancer risk. Nevertheless, more studies are necessary to establish whether this mutation has a role in breast cancer risk.
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PMID:An intronic variant in the TP53 gene in a Brazilian woman with breast cancer. 1599 72

Breast cancer is the most common malignancy which affects women. In 5-10% of all cases, breast cancer presents as a hereditary cancer syndrome. Since 1996, 68 families with suspicion of familial breast cancer have been referred to our department. In 5 of the 68 families (7.4%), the clinical diagnosis was hereditary breast ovarian cancer syndrome. In 17 families (25%), two or more breast cancer cases were present. Mutation screening of BRCA1 and BRCA2 in these families revealed a BRCA1 mutation (185delAG) in one family. Three families (4.4%) had a diagnosis of Li-Fraumeni syndrome and germline mutations in TP53 (Lys292Ile, Pro278Ser and Pro278Thr). Breast cancer occurred in a family with hereditary nonpolyposis colon carcinoma (HNPCC; Lynch syndrome) carrying an MLH1 mutation (IVS17-3G>C). Most of our families (41 families; 60.2%) had only one case with breast cancer or cystic adenoma (or both) and did not need counseling and DNA testing. In summary, in 10 of the 68 families in our series (14.7%), a germline mutation in a breast cancer predisposing gene was detected. Our data show the importance of detailed examination of clinical data, pedigree analyses, and molecular germline diagnostics for the counseling of breast cancer cases.
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PMID:Hereditary breast cancer syndromes in a Turkish population. Results of molecular germline analysis. 1599 73

Li-Fraumeni syndrome is a rare cause of breast cancer. It should be considered in cancer cases where a genetic link is suspected. It impacts dramatically on treatment and has major implications for the patient and their family.
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PMID:Li-Fraumeni syndrome: a case report and discussion. 1616 4

The tumor suppressor gene p53 has an apparent role in breast tumor development in humans, as approximately 30% of sporadic tumors acquire p53 mutations and Li-Fraumeni syndrome patients carrying germ line p53 mutations frequently develop breast tumors at early age. In the present study, conditional expression of a targeted mutation is used to analyze the role of the human R273H tumor-associated hotspot mutation in p53 in mammary gland tumorigenesis. Heterozygous p53(R270H/+)WAPCre mice (with mammary gland-specific expression of the p53.R270H mutation, equivalent to human R273H, at physiologic levels) develop mammary tumors at high frequency, indicating that the R270H mutation predisposes for mammary gland tumor development and acts in a dominant-negative manner in early stages of tumorigenesis. Spontaneous tumor development in these mice is further accelerated by 7,12-dimethylbenz(a)anthracene (DMBA) treatment at young age. The majority of spontaneous and DMBA-induced carcinomas and sarcomas from p53(R270H/+)WAPCre mice is estrogen receptor alpha positive, and expression profiles of genes also implicated in human breast cancer appear similarly altered. As such, p53(R270H/+)WAPCre mice provide a well-suited model system to study the role of p53 in breast tumorigenesis and the responsiveness of mammary gland tumors to chemotherapeutics.
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PMID:Mice expressing a mammary gland-specific R270H mutation in the p53 tumor suppressor gene mimic human breast cancer development. 1616 91

Li-Fraumeni syndrome (LFS) is an autosomal-dominant condition characterized by early-onset sarcoma, breast cancer and other specific tumour types. In most LFS kindreds germline TP53 mutations have been identified. In general, TP53 germline mutations are not associated with late-onset common cancers. We encountered a large kindred in which a wide spectrum of tumour types occurred, including melanoma, breast, ovarian, colorectal, stomach and renal cell cancer, without clear-cut early ages at onset of disease. An Arg213Gln TP53 germline mutation was detected in 12 out of 15 affected family members whereas testing for other cancer susceptibility genes in selected patients was negative. In vitro testing indicated that the specific TP53 mutation inactivates the protein transcriptionally. Our findings suggest that this TP53 germline mutation is a causative factor in this family and that specific TP53 germline mutations can be associated with relatively late-onset common cancers.
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PMID:Late-onset common cancers in a kindred with an Arg213Gln TP53 germline mutation. 1673 87

We used the nation-wide Swedish Family-Cancer Database to examine the familial risks of histology-specific bone cancers in offspring by parental or sibling probands. Adjusted standardised incidence ratios (SIRs) were used to measure the risk. Among the 1327 offspring bone cancers, only two parent-offspring pairs and one sibling pair were noted with concordant bone cancer but the SIRs were not significant. Significant associations were observed in specific histological types or specific age groups, some of which may be chance findings arising from multiple comparisons. However, the risk of early-onset (< 25 years) osteosarcoma in offspring was significantly increased when mothers presented with breast cancer (1.7) and melanoma (2.9), suggesting that Li-Fraumeni syndrome could partly explain this familial aggregation. Other associations, such as childhood osteosarcoma with parental liver cancer, Ewing's sarcoma with kidney cancer and giant cell sarcoma with maternal breast cancer, were novel findings and may be related to other familial diseases.
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PMID:Familial risk for histology-specific bone cancers: an updated study in Sweden. 1685 7

Li-Fraumeni syndrome (LFS) is a very rare autosomal dominant and highly penetrant cancer syndrome characterized by early-onset primary tumours, including soft tissue and bone sarcoma, breast cancer, leukemia, brain tumours and adrenocortical carcinoma. Here we report the first evidence-based case of LFS in Bosnia and Herzegovina and the whole Balkan region. A ten year-old girl developed multiple primary tumours (rhabdomyosarcoma) during a period of eight years, as well as fibroadenoma of the breast. Sequential analysis revealed a germ line mutation of TP53 in exon 8, a common mutation in patients with LFS, in both the patient and her mother.
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PMID:The first case of Li-Fraumeni syndrome in Bosnia and Herzegovina: case report. 1692 90

The genetic aetiology of familial aggregations of breast cancer and sarcomas has been elucidated only in part. In this study, 23 unrelated individuals from families with one case of sarcoma and at least one case of breast cancer were screened for mutations in the TP53, BRCA1 and BRCA2 genes. Families were classified according to their conformity to the criteria defining the Li-Fraumeni syndrome (LFS), Li-Fraumeni-like (LFL) syndrome and hereditary breast/ovarian cancer (HBOC). Germline TP53 mutations were identified in three instances (13%), including one LFS and two LFL families, while none of the non-LFS/non-LFL families had a TP53 mutation. Three cases (13%), including one with a TP53 mutation, carried BRCA2 mutations. Of these, two were observed in LFL/HBOC families and the other one in a non-LFS/non-LFL/HBOC family, while none of the non-HBOC families tested positive. These findings suggest that the screening of BRCA2, in addition to TP53, may be appropriate for the molecular characterisation of breast cancer/sarcoma families, with practical implications for counselling and clinical management.
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PMID:Germline mutations of TP53 and BRCA2 genes in breast cancer/sarcoma families. 1722 68


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