What is being tested?
BRCA1 and BRCA2 are two tumour suppressor genes. Normally, these genes help prevent cancer by producing proteins that repair damage to DNA (the genetic material in a cell). Certain changes (pathogenetic variants) in these genes disrupt the function of the protein product and are associated with hereditary breast and ovarian cancers.
According to Cancer Australia, using statistics from the Australian Institute of Health and Welfare, over 19,000 women in Australia are diagnosed with breast cancer each year and about 1,500 women with ovarian cancer. In most of these women, their cancers are sporadic, but about 5-10% of these women have a familial predisposition to breast/ovarian cancer. Approximately 20% of the familial breast/ovarian cancers (i.e. 1-2% overall) are due to a genetic fault (pathogenetic variant) in the BRCA1 or BRCA2 gene. Men can also inherit an increased risk of developing breast cancer, occasionally from pathogenetic variants in BRCA1, but primarily from pathogenetic variants in the BRCA2 gene.
The BRCA1 and BRCA2 genes are present in every cell of the body. To detect pathogenetic variants in these genes, DNA needs to be extracted from cells, and blood is the most easily accessible source of that DNA.
How is it used?
There are thousands of different BRCA1 and BRCA2 genetic faults (pathogenetic variants) that have been reported. In families with a strong family history of breast/ovarian cancer, it is usually necessary to first test an affected family member to determine whether the predisposition to breast/ovarian cancer in the family is due to a BRCA1/2 fault, and if so, what the particular fault (pathogenetic variant) is. This is known as diagnostic testing. Once the ‘familial variant’ is found, other family members can then be tested for that specific variant to determine their personal cancer risk. This is known as predictive (or pre-symptomatic) testing, and is only offered through a family cancer clinic. Predictive (or pre-symptomatic) testing is helpful in deciding whether to take steps such as prophylactic surgery that may reduce the likelihood of developing breast or ovarian cancer in the future.
When is it requested?
If a BRCA1 or BRCA2 genetic fault (pathogenetic variant) has been identified in a family member with breast and/or ovarian cancer, then other family members can be tested for that specific variant to assess their risk.
Specific BRCA1 and BRCA2 variants are associated with some ethnic groups, such as those of Ashkenazi Jewish descent, and can be used to evaluate the risk of individuals in this group.
Someone who is considering testing should talk to their healthcare practitioner and seek genetic counselling by a genetics educator/counsellor prior to and after testing.
What does the result mean?
The degree of risk conferred with a positive result is difficult to quantify for a specific person. Results must be interpreted in conjunction with the tested person's personal and family history. A genetic counsellor or familial cancer specialist should explain the meaning of the results, explain treatment options for the individual that are intended to decrease risk, and testing options for other family members.
The presence of a genetic fault (pathogenic variant) in BRCA1 or BRCA2 means that the person tested is at an increased risk for breast and/or ovarian cancer, but it does not mean that they will definitely develop cancer. Even within a family with the same BRCA1/2 variant, not everyone will develop cancer and those that do may develop it at different times during their life. The lifetime risk for breast cancer in women with a pathogenic BRCA1/2 variant is estimated to be up to about 70% (1). The risk of ovarian cancer is about 44% with a pathogenic BRCA1 variant and 17% with a pathogenic BRCA2 variant (1).
A negative result does not mean that an individual will not develop breast or ovarian cancer. It simply indicates that the person tested is not at increased risk for developing hereditary breast cancer or ovarian cancer related to the BRCA 1/2 variants for which he/she was tested. It is important to remember that more than 95% of breast cancers are not associated with a pathogenic BRCA1/2 variant. Furthermore, in the general population, the lifetime risk of developing breast cancer is approximately 12% and the lifetime risk of developing ovarian cancer is about 1%.
Is there anything else I should know?
Genetic testing of BRCA1 and BRCA2 cannot detect 100% of pathogenic variants in these genes; thus, even with a negative result there is a very small chance that there is a BRCA1/BRCA2 variant present that was not identified by the testing method utilised. For negative results, a genetic counsellor or specialist will provide tailored advice based on the individual’s personal and family history.
Genetic variants in other genes can also be associated with a familial risk for cancer so the specialist or consultant physician may offer testing of other genes besides BRCA1 and BRCA2. When deciding which genes to assess, the specialist will take into consideration factors such as the age at which the cancer was diagnosed, specific characteristics of the cancer, and whether other close family members have also been diagnosed with certain types of cancer previously.
Positive test results may have implications for other family members. When one member of a family is tested for BRCA 1/2 variants, issues often arise about how or whether to share this information with other family members. Seek advice from a genetic counsellor about communication of results with other family members.
Pre- and post-test consultation with a health care provider knowledgeable about genetic testing cannot be overemphasised. There are many issues to be considered when preparing for a genetic test and upon learning the results, and a genetic counsellor has the knowledge and expertise to help sort through them.
Common questions
If the BRCA mutation test is positive, the options include more frequent cancer screenings and screening starting earlier in life (e.g., mammography, breast MRI, blood tests for CA-125 or CA 15-3, or transvaginal ultrasonography), medications that could reduce risk (e.g., tamoxifen), or surgical removal of the ovaries or breasts. There are a number of variables involved and it is important to discuss your options with your healthcare provider and genetic counsellor.
See the previous section “What does the test result mean?”
A negative result does not completely exclude the possibility of developing breast or ovarian cancer. See the previous section ‘What does the test result mean?’ for more information.
The test can be requested by specialists in familial cancer clinics or clinical geneticists if it is considered appropriate and should be accompanied by pre- and post-test genetic counselling. These services are available across Australia, and can be accessed by referral from your general practitioner. The blood sample will be sent to a laboratory that specialises in genetic testing.
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