Who Should Get BRCA Tested
Women with a personal or family history suggesting inherited cancer susceptibility should undergo BRCA testing after appropriate genetic counseling, while routine testing is not recommended for those without such risk factors. 1
Primary Indications for BRCA Testing
Personal History Criteria
Women should be offered BRCA testing if they have:
- Breast cancer diagnosed at age ≤45 years 2, 3
- Breast cancer diagnosed at age ≤50 years with one or more close blood relatives with breast cancer 2, 3
- Triple-negative breast cancer diagnosed before age 50 2
- Two primary breast cancers, especially when the first occurred before age 50 2, 3
- Epithelial ovarian, fallopian tube, or primary peritoneal cancer at any age 2, 3, 4
- Male breast cancer, regardless of family history 2, 3
- Breast cancer at any age with two or more close blood relatives with breast and/or ovarian cancer 2, 3
Family History Criteria
Testing should be considered when family history includes:
- Breast cancer before age 50 years in family members 1
- Bilateral breast cancer in the family 1
- Both breast and ovarian cancer in the family 1
- Breast cancer in one or more male family members 1
- Multiple cases of breast cancer in the family 1
- One or more family members with two primary types of BRCA-related cancer 1
- A first- or second-degree blood relative meeting any personal history criteria 2, 3
- A known BRCA mutation in a family member 2, 3
Ethnic Background Considerations
Ashkenazi Jewish women have specific criteria:
- Breast cancer diagnosed before age 60 2
- Ovarian or pancreatic cancer at any age 3, 5
- Less stringent testing criteria apply due to higher prevalence of founder mutations (approximately 1 in 40 carry a BRCA mutation) 6
Risk Assessment Tools for Primary Care
Primary care providers should use brief familial risk stratification tools to identify women needing genetic counseling. 1 The USPSTF-evaluated tools include:
- Ontario Family History Assessment Tool 1
- Manchester Scoring System 1
- Referral Screening Tool (B-RST) 1
- Pedigree Assessment Tool 1
- Family History Screen-7 (FHS-7) 1
The Referral Screening Tool and FHS-7 are the simplest and quickest to administer, with sensitivity estimates >85%. 1 However, no single tool has been proven superior, and the USPSTF found insufficient evidence to recommend one over another. 1
Important caveat: Do not use general breast cancer risk assessment models like the Gail model, as they are not designed to determine who needs BRCA testing. 1
Who Should NOT Be Routinely Tested
The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history is not associated with potentially harmful BRCA mutations. 1, 5 For these women, the net benefit ranges from minimal to potentially harmful. 1
Testing Strategy and Approach
Optimal Testing Sequence
Initial testing should be performed on an affected family member with breast or ovarian cancer whenever possible. 1 This strategy maximizes the likelihood of detecting a clinically significant mutation. 1
If no affected relative is available for testing, it is reasonable to test an unaffected individual, though interpretation of negative results becomes more challenging. 1, 3
Ashkenazi Jewish-Specific Testing
For Ashkenazi Jewish individuals, initial testing for the three common founder mutations (185delAG, 5382insC in BRCA1, and 6174delT in BRCA2) is recommended. 1, 3, 6
If founder mutation testing is negative but other criteria are met, full sequence testing should be considered. 1, 3
When to Begin Screening
Consideration of screening for BRCA mutations should begin once women reach age 18 (age of consent). 1
Primary care providers should periodically reassess family history, with comprehensive review at least every 5 to 10 years, as new cancer diagnoses may emerge. 1
Pre-Testing Requirements
Genetic counseling must be provided before testing. 1 The counseling process should include:
- Detailed kindred analysis and risk assessment 1
- Education about possible test results and their implications 1, 2
- Identification of affected family members who may be preferred candidates for testing 1
- Discussion of screening options, risk-reducing medications, and surgery 1
- Psychological impact, cost, insurance, and privacy considerations 2
Testing should only proceed when the individual is fully informed and has expressed desire for it. 1
Understanding Test Results
Test interpretation is complex and requires posttest counseling. 1 Results fall into four categories:
- Positive (pathogenic mutation detected): Confirms inherited cancer susceptibility 1
- Variant of uncertain significance: Should not be used for clinical decision-making 2
- True-negative: Occurs when a known familial mutation is absent; breast cancer risk is generally not increased 1
- Uninformative-negative: No mutation detected but no relatives tested or no mutations found in tested relatives; breast cancer risk remains increased 1
Critical Pitfalls to Avoid
Do not delay cancer treatment to wait for genetic testing results. 3 Testing can be incorporated into the treatment planning process without causing delays.
Recognize that approximately 33% of BRCA mutation carriers have no family history of breast or ovarian cancer in first or second-degree relatives. 6 Conversely, 12% of non-carriers have strong family histories. 6 This underscores why family history alone is insufficient for decision-making.
Universal testing for all women with high-grade serous ovarian carcinoma is now recommended, as family history-based criteria would miss 24% of those with pathogenic variants. 4 This represents a shift from traditional genetics-based testing models.
Age at diagnosis may be a stronger predictor of testing need than family history alone. 7 Young women diagnosed before age 50 have nearly five times the odds of carrying a mutation compared to those diagnosed at age 50 or older, even without significant family history. 7
For women diagnosed with breast cancer, BRCA mutations are associated with a 10-fold increased risk of subsequent ovarian carcinoma. 8 This makes testing particularly important for treatment and surveillance planning.