Genetic Testing for Breast and Ovarian Cancer Susceptibility: A Family Experience

Marcia Van Riper, RN, PhD


J Midwifery Womens Health. 2004;49(3) 

In This Article

History of Genetic Testing for Breast and Ovarian Cancer Susceptibility

It is estimated that 5% to 10% of all breast and ovarian cancers are hereditary cancers[15,16] and can be attributed to inheritance of a mutation in a gene associated with breast and ovarian cancer susceptibility, such as BRCA1, BRCA2, TP53, and pTEN.[17] Another 15% to 20% of female breast cancers occur in women who have a strong family history of breast and ovarian cancer but do not carry one of the known mutations associated with breast and ovarian cancer susceptibility.[18]

BRCA1, the first gene associated with breast and ovarian cancer susceptibility to be identified, was mapped on chromosome 17 in 1990 and cloned in 1994.[19] The second major gene associated with breast and ovarian cancer susceptibility, designated as BRCA2, was mapped on chromosome 13 in 1994 and cloned in 1995.[20] BRCA2 is twice as large as BRCA1. The precise nature of the contribution of BRCA1 and BRCA2 remains a mystery, but these genes encode for very large proteins that have been implicated in a number of processes fundamental to all cells, including DNA repair and recombination, checkpoint control of cell cycle, and transcription.[21] Mutations in the BRCA1 and BRCA2 genes are inherited in an autosomal dominant pattern, so each offspring of an individual found to carry one of these mutations has a 50% chance of carrying the same mutation. More than 2,000 distinct mutations and sequence variations BRCA1 and BRCA2 genes have been identified. Most of these mutations truncate the protein product.[22] However, some of these mutations are missense mutations that alter a single amino acid. Overall, mutations in BRCA genes account for approximately 70% of hereditary breast and ovarian cancers.[23]

Genetic testing for BRCA1 and BRCA2 mutations is commercially available through Myriad Genetics, a private company that holds at least 17 patents worldwide on BRCA mutation testing.[24] The cost for this testing ranges from around $2,760 for full sequencing of the BRCA1 and BRCA2 genes to $325 for an analysis of a single mutation site in relatives of an individual with an identified mutation. The cost for an analysis of three mutations (185delAG, 5382insC, and 6174delT) commonly found in individuals of Ashkenazi Jewish descent is $385. Although many health insurance plans will pay all or part of the cost of genetic testing for BRCA mutations, some individuals choose to self-pay because they are afraid of insurance and employment discrimination.[25] Others apply for assistance from the Myriad Financial Assistance (Hardship) Program or charitable organizations, such as local and state breast cancer support programs. Individuals and families involved in research concerning BRCA mutations may be able to get BRCA testing done at little or no cost. In 2000, an agreement was made between the National Cancer Institute and Myriad Genetics to offer researchers funded by the National Institutes of Health access to full BRCA sequencing for $1,200 per person.[26]

On the basis of preliminary reports, it was predicted that there would be strong interest in BRCA testing (72%-91%), both in the general population and for high-risk families.[27,28,29] To date, actual uptake has been less than was predicted.[30,31] In a recent study of women at average risk for breast cancer,[32] 41% of the women indicated that they probably or definitely would pursue BRCA testing. Press and colleagues[33] found that interest in genetic testing for breast cancer susceptibility appeared to be shaped by an exaggerated sense of vulnerability to breast cancer, limited knowledge about genetic susceptibility testing, and generally positive views about information provided through medical screening. Participants in the study were most interested in a genetic test that does not exist (high positive predictive value followed by effective, non-invasive treatment) and were less interested in the genetic test for breast cancer susceptibility that does exist (less than certain positive predictive value, low negative predictive value, and limited, invasive, and objectionable therapeutic options). These findings suggest that women at average risk for breast cancer may not be aware of the limitations of the genetic testing for breast cancer susceptibility that is currently being offered.


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