In addition, the FHAT includes colon and prostate cancer, while the Manchester, BOADICEA and Penn II models include prostate and pancreatic cancer. All models incorporate a family history of breast and ovarian cancer. Each model calculates risk on the basis of the inclusion of different cancer diagnoses within a family. The Manchester, Penn II, IBIS and BOADICEA models were developed more recently. BRCAPRO, Myriad II, Couch and FHAT were among the first risk models developed and have been in clinical use for a number of years through CaGene software. The BRCAPRO, Myriad II, Couch (also known as Penn), Family History Assessment Tool (FHAT), Manchester, Penn II, IBIS, and Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) models have all been developed to predict the probability of identifying germline BRCA mutations in an individual or a family. This can involve a review of a detailed three-generation pedigree by a specialist, and also a risk calculation using validated risk assessment models. A family history assessment is crucial for this process. Given that funding for genetic testing is limited and that BRCA mutations are rare even in the referred population, the challenge remains to identify those individuals most likely to carry a mutation prior to offering genetic testing. Health care providers refer patients to these programs because of a family history of cancer. Patients gain access to BRCA testing through familial cancer genetics programs.
Knowledge of a hereditary predisposition can significantly alter medical management and follow-up for carriers, regardless of previous cancer history, and may allow access to healthcare resources not widely available to individuals at general population risk. Mutation carriers are offered intensified surveillance for early detection, chemoprevention and risk-reducing surgeries. Individuals with known BRCA mutations are managed differently from the general population. In Ontario, Canada, the testing methodology changed in 2007 from protein truncation testing (PTT) with sequencing of exons 2 and 5 of BRCA1, to the currently-used DHPLC and multiplex ligation-dependent probe assay (MLPA). In other areas of the world, denaturing high performance liquid chromatography (DHPLC) is the method used for detecting mutations. In the United States, testing is commonly performed by gene sequencing and large deletion and rearrangement screening. Various methodologies have been developed to identify mutations in BRCA1 and BRCA2, and numerous studies have been performed to evaluate the benefits and limitations of each method. Also, there may be increased risks of other cancers such as male breast cancer, melanoma, pancreas and prostate cancer associated with BRCA mutations. However, there are discrepancies in risk estimates, as previous studies have shown breast cancer risks of 56–87% and ovarian cancer risks of 10–40%. Most recent risk estimates from a large United States sample suggest that breast cancer risks up to age 70 for BRCA1 and BRCA2 mutation carriers are 43% and 46% respectively, and ovarian cancer risks are 39% and 22% respectively. These risks probably depend on family history, the population under study and the mutation type. Other syndromes such as Li-Fraumeni syndrome, PTEN mutation-associated syndromes and heterozygous Ataxia Telangiectasia account for less than 5% of hereditary breast cancers.Ĭancer risks associated with BRCA1 and BRCA2 mutations have been well documented, but are varied. Most breast cancers known to be hereditary are attributable to HBOC. The syndrome associated with BRCA mutations is termed Hereditary Breast and Ovarian Cancer (HBOC). Population-based studies have shown that mutations in BRCA1 and BRCA2 confer an increased risk of breast, ovarian and other cancers. In 1990, the BRCA1 gene was mapped to chromosome 17 by genetic linkage analysis, and the BRCA2 gene was subsequently identified and mapped to chromosome 13. Although the specific etiology of breast cancer is unknown, hormonal, reproductive and hereditary factors have all been shown to be risk factors.Īmong the hereditary factors involved in breast cancer, single gene mutations contribute a significant increase in risk. Statistics for the year 2007 showed that 1 in 9 women will be diagnosed with the disease and 1 in 27 women will die of it.
Breast cancer is the most frequently diagnosed cancer among women in North America.
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