Table 1
BRCA1/2 associated cancer risks.
| Cancer Type | General Population Risk | Mutation Risk | |
|---|---|---|---|
| BRCA1 | BRCA2 | ||
| Breast | 12% | 50%-80% | 40%-70% |
| Second primary breast | 3.5% within 5 years Up to 11% | 27% within 5 yrs | 12% within 5 yrs 40%-50% at 20 yrs |
| Ovarian | 1%-2% | 24%-40% | 11%-18% |
| Male breast | 0.1% | 1%-2% | 5%-10% |
| Prostate | 15% (N. European origin) 18% (African Americans) | <30% | <39% |
| Pancreatic | 0.50% | 1%-3% | 2%-7% |
Table 2
Elements of informed consent for genetic testing of cancer susceptibility [39].
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Table 3
Nccn testing criteria [16].
|
National Comprehensive Cancer Network, v3.2013
** One or more of these criteria is suggestive of hereditary breast/ovarian cancer syndrome that warrants further personalised risk assessment, genetic counselling, and often genetic testing and management. The maternal and paternal sides should be considered independently. Melanoma has been reported in some hereditary breast/ovarian cancer families.
•• Patients who have received an allogeneic bone marrow transplant should not have molecular genetic testing via blood or buccal samples due to unreliable test results from contamination by donor DNA. If available, DNA should be extracted from a fibroblast culture. If the source of DNA is not possible, buccal samples can be considered, subject to the risk of donor DNA contamination.
ΔΔ Individuals with a limited family history, such as fewer than two first- or second-degree female relatives or female relatives surviving beyond 45 years in either lineage, may have an underestimated probability of a familial mutation.
♢♢ For the purposes of these guidelines, invasive and ductal carcinoma in situ breast cancers should be included.
§§ Two breast primaries include bilateral (contralateral) disease or two or more clearly separate ipsilateral primary tumors either synchronously or asynchronously.
¥¥ Testing for Ashkenazi Jewish founder-specific mutation(s) should be performed first. Full sequencing may be considered if ancestry also includes non-Ashkenazi Jewish relatives or other hereditary breast/ovarian cancer criteria are met. Founder mutations exist in other populations.
‡‡ Clinical judgement should be used to determine if the patient has reasonable likelihood of mutation, considering the unaffected patient’s current age and the age of the female unaffected relatives who link the patient with the affected relatives. Testing of unaffected individuals should only be considered when an appropriate affected member is unavailable for testing. Significant limitations of interpreting test results for an unaffected individual should be discussed.