Hereditary breast and ovarian cancer syndrome (HBOC) is associated with germline mutations in the BRCA1 and BRCA2 (BRCA1/2) genes. It is estimated that 2-7% of breast cancers, and 10-15% of ovarian cancers are the result of an inherited mutation in one of these two genes.
It is estimated that 1/300 individuals in the general population carry a mutation in BRCA1/2. Among individuals of Ashkenazi Jewish descent, this number is as high as 1/40. Women who carry a BRCA1/2 mutation have a lifetime risk for breast cancer of 50-80% and a lifetime risk for ovarian cancer of 10-40%. Unfortunately, the vast majority of individuals who carry BRCA1/2 mutations have not yet been identified, and when they are, it is often because of a diagnosis of breast and ovarian cancer.
In 2005 and 2014 the United States Preventive Services Task Force (USPSTF) published grade B recommendations endorsing screening women for possible HBOC risk, emphasizing those identified at increased risk should receive genetic counseling and, if indicated after counseling, BRCA testing. Please click the following link to learn more about genetic counseling services.
The B-RST has been endorsed by the USPSTF as one of several validated screening tools that are clinically useful predictors for determining which women need to be referred for cancer genetic counseling. B-RST is simple, quick and provides accurate results in identifying individuals at potential risk for HBOC.
The B-RST tool was originally validated in a population of 2,464 unselected women undergoing screening mammography. When compared to complex models requiring detailed four-generation family history information, BRST demonstrated an overall discriminative accuracy of 0.90 (95% CI 0.86-0.95) in identifying women with a ≥10% probability of carrying a BRCA1/2 mutation (sensitivity 89%, specificity 92%). Based on changing data,the B-RST algorithm was recently revised (B-RST 3.0) and re-evaluated in a large cohort tested for BRCA1/2 mutations. B-RST 3.0 was found to have an sensitivity of 93% to identify individuals with a BRCA1/2 mutation, while maintaining a specificity significantly higher than that of the NCCN guidelines. Women who screen positive on B-RST, but are not appropriate candidates for genetic testing, typically are at moderate increased risk for breast cancer based on their family history, and may benefit from consideration of enhanced screening or chemoprevention.
Recently, genetic testing trends for individuals at-risk for hereditary breast and/or ovarian cancer have included the use of panels, which evaluate other hereditary cancer genes beyond BRCA1/2. Though not designed to screen for these other syndromes, a positive B-RST screen would be expected to also identify a portion of individuals with other hereditary cancer syndromes. Note that many of the genes on these panels are associated with moderate or uncertain risks, and data is limited regarding best management strategies.
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