Who Should Be Tested for BRCA Mutation
All women with nonmucinous epithelial ovarian, fallopian tube, or primary peritoneal cancer should be offered BRCA1/2 testing, regardless of age or family history. 1, 2
Personal History Criteria for Testing
Breast Cancer Patients
Women diagnosed with breast cancer at age ≤45 years should undergo genetic testing. 3
Women diagnosed with breast cancer at age 46-50 years should be tested if they have at least one close blood relative with breast cancer at any age. 3
Triple-negative breast cancer diagnosed before age 50 years (or age ≤60 years per some criteria) is an indication for testing. 1, 3
Two primary breast cancers in the same individual, especially when the first diagnosis occurred before age 50, warrants testing. 3
Male breast cancer at any age is a criterion for genetic testing, regardless of family history. 1, 3, 4
Ovarian and Related Cancers
All women with nonmucinous epithelial ovarian cancer should be offered BRCA testing, ideally at diagnosis. 1, 2
Fallopian tube and primary peritoneal cancers at any age are indications for testing. 1, 3
Testing should be offered even to patients in long-term follow-up due to implications for family members and individual future breast cancer risk. 2
Family History Criteria for Testing
High-Risk Family Patterns
Three or more breast and/or ovarian cancer cases on the same side of the family, with at least one diagnosed before age 50, indicates testing. 1, 3
Two breast cancer cases in close relatives diagnosed before age 40 warrants testing. 1, 3
Individuals with a first- or second-degree blood relative meeting any personal history criteria should be tested. 3
A known mutation in a breast cancer susceptibility gene in a family member is an indication for testing. 3
Syndromic Presentations
- Breast cancer at any age combined with family history of thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumors, diffuse gastric cancer, or leukemia/lymphoma indicates testing. 3
Ethnic Background Considerations
Ashkenazi Jewish individuals with breast cancer diagnosed before age 60 years should be tested. 1, 3
Ashkenazi Jewish individuals with pancreatic cancer at any age should be considered for testing. 1
For Ashkenazi Jewish individuals, initial testing for the three common founder mutations is recommended, followed by full sequence testing if negative but other criteria are met. 3
Testing Approach and Timing
Optimal Testing Strategy
Testing should begin with an affected family member who has the highest likelihood of carrying a mutation. 1, 3
If no living affected family member is available, testing unaffected relatives is reasonable with appropriate counseling about limitations. 1, 3
For ovarian cancer patients, germline BRCA testing of blood/saliva should be conducted first; if negative, tumor tissue should be tested to identify somatic BRCA mutations. 2
Age Considerations
Consideration of screening for potentially harmful BRCA mutations should begin once women reach age 18 years (age of consent). 1
Primary care providers should periodically assess all patients for changes in family history, with comprehensive review at least every 5-10 years. 1
Risk Assessment Models
Probability models such as BRCAPRO, BOADICEA, and Manchester Score can guide testing decisions. 1, 3
Testing is often considered when there is a 10-20% probability of finding a mutation based on these models. 1, 3
Pre-Testing Requirements
Genetic Counseling Essentials
Genetic counseling must be provided before testing to discuss benefits, risks, and limitations. 1, 3
Counseling should include discussion of the probability of finding a mutation, implications for the individual and family, and meaning of variants of uncertain significance or null results. 1
Testing should only be done when an individual has access to a health professional trained to provide genetic counseling and interpret test results, and when test results will aid in decision making. 1
Testing must be voluntary and the individual or their legal proxy must provide informed consent. 1
Common Pitfalls to Avoid
Do not wait for extensive family history in ovarian cancer patients—all nonmucinous epithelial ovarian cancers warrant testing regardless of family history. 1, 2
Do not test unaffected family members first when an affected relative is available for testing, as this may yield uninformative results. 1
Do not use variants of uncertain significance for clinical decision-making. 3
Do not assume true-negative results eliminate all breast cancer risk—women with uninformative-negative results (no mutation detected but no relatives tested) remain at increased risk. 1
Do not limit testing to BRCA1/2 alone in appropriate candidates—fewer than one-third of excess breast cancers in young patients are BRCA1/2-related, suggesting other genes may be involved. 5