The BRCA1 and BRCA2 genes repair damaged DNA, acting as tumor suppressors to prevent uncontrolled cell growth. Inherited changes or “mutations” in these genes impair their function, significantly increasing a person’s lifetime risk for certain cancers, including breast, ovarian, prostate, and pancreatic cancers. Understanding these genes is important for individuals considering genetic testing to assess their personal cancer risk.
Considerations for BRCA Gene Testing
Deciding whether to pursue BRCA gene testing involves evaluating personal and family health histories. Healthcare providers often recommend testing for individuals with a personal history of certain cancers, including:
Breast cancer diagnosed before age 50
Triple-negative breast cancer at any age
Breast cancer in both breasts
A combination of breast and ovarian cancer at any age
Male breast cancer at any age
Ovarian, fallopian tube, or peritoneal cancer
Family history also provides significant clues for BRCA testing eligibility, such as:
Multiple relatives on the same side of the family diagnosed with breast cancer (especially before age 50)
One or more relatives with ovarian cancer at any age
Male breast cancer within the family
Multiple cases of prostate cancer within the family
Pancreatic cancer within the family
A close relative identified with a BRCA mutation
Certain ethnic backgrounds, such as Ashkenazi Jewish ancestry, are associated with a higher prevalence of BRCA mutations, making testing a consideration even without an extensive family history. The decision to undergo BRCA gene testing is personal and should be made after discussion with a healthcare professional or genetic counselor.
Interpreting BRCA Test Results
After undergoing BRCA gene testing, there are typically three possible outcomes, each with distinct implications. A “positive result,” also referred to as a pathogenic or likely pathogenic variant, indicates that a harmful mutation in the BRCA1 or BRCA2 gene has been identified. This means the individual has an increased lifetime risk of developing specific cancers, such as breast, ovarian, and potentially prostate or pancreatic cancer. However, a positive result does not guarantee that cancer will develop; it signifies an elevated predisposition.
A “negative result,” or benign/likely benign variant, means that no known harmful mutation in BRCA1 or BRCA2 was found. If no specific mutation was known in the family, this suggests the individual’s risk for BRCA-related cancers is similar to that of the general population. If a specific BRCA mutation was previously identified in a family member and the individual tests negative for that particular mutation, it implies they did not inherit the familial mutation. It is important to remember that a negative BRCA test does not eliminate all cancer risk, as other genetic or lifestyle factors can still contribute to cancer development.
The third possible outcome is a “Variant of Uncertain Significance” (VUS). This result indicates a change in the gene sequence has been detected, but its impact on cancer risk is currently unknown. VUS results are often not immediately clinically actionable and typically do not alter medical management initially. These variants require further research and may be reclassified over time as more scientific data becomes available, and laboratories may issue updated reports.
Next Steps After BRCA Gene Testing
Following BRCA gene testing, the recommended next steps depend on the specific results received. For individuals with a positive BRCA mutation, management focuses on heightened surveillance and risk reduction strategies. Enhanced breast cancer screening is typically recommended, often beginning at a younger age, and may include annual MRIs and mammograms. Options for risk-reducing surgeries, such as prophylactic mastectomy to lower breast cancer risk or salpingo-oophorectomy to reduce ovarian and breast cancer risk, are discussed with a healthcare team. Additionally, certain chemoprevention medications, such as tamoxifen or anastrazole, may be considered to reduce the risk of estrogen receptor-positive breast cancer, particularly for those with a BRCA2 mutation.
For men with BRCA mutations, particularly BRCA2, prostate cancer screening with annual PSA testing may be recommended starting around age 40, and participation in prostate cancer screening trials could be an option. A genetic counselor plays a significant role in helping individuals understand their positive results and explore personalized risk management plans. They can also discuss implications for family members, who may also consider testing.
If test results are negative and no specific family mutation was identified, individuals generally follow standard cancer screening guidelines for the general population. While the BRCA-related risk is not elevated, other cancer risks remain. For those with a Variant of Uncertain Significance (VUS), the typical approach is to monitor the variant as research progresses. These results are usually not used to guide immediate medical decisions, and individuals are encouraged to check with their healthcare provider periodically for updates on the classification of the VUS.