Criteria for Genetic Testing for Breast Cancer
Genetic testing for breast cancer should be offered to individuals who meet specific family history and personal criteria that indicate an elevated risk of hereditary breast cancer syndromes.
Personal History Criteria
- Breast cancer diagnosed at age ≤45 years 1
- Breast cancer diagnosed at age ≤50 years with one or more close blood relatives with breast cancer at any age 1
- Two primary breast cancers in the same individual, especially when the first breast cancer diagnosis occurred before age 50 1
- Triple-negative breast cancer diagnosed at age <50 years 1
- Personal history of epithelial ovarian, fallopian tube, or primary peritoneal cancer at any age 1
- Personal history of male breast cancer 1, 2
- Breast cancer at any age with two or more close blood relatives with breast and/or ovarian cancer at any age 1
- Breast cancer with a close male blood relative with breast cancer 1
Family History Criteria
- First- or second-degree blood relative meeting any of the personal history criteria above 1
- Three or more breast and/or ovarian cancer cases on the same side of family (maternal or paternal), with at least one diagnosed before age 50 1
- Two breast cancer cases in close relatives diagnosed before age 40 1
- A combination of breast cancer with one or more of the following in close relatives: thyroid cancer, sarcoma, adrenocortical carcinoma, endometrial cancer, pancreatic cancer, brain tumors, diffuse gastric cancer, or leukemia/lymphoma 1
- Family member with a known mutation in a breast cancer susceptibility gene (BRCA1, BRCA2, etc.) 1
Ethnic Background Considerations
- Ashkenazi Jewish descent with breast cancer diagnosed at age <60 years 1
- Ashkenazi Jewish descent with breast or ovarian cancer at any age (may have less stringent testing criteria due to higher prevalence of founder mutations) 1, 3
Testing Approach
- Testing should begin with an affected family member who has the highest likelihood of carrying a mutation (youngest age at diagnosis, bilateral disease, multiple primaries, or ovarian cancer) 1
- If no living affected family member is available, testing unaffected relatives should be considered with appropriate counseling about limitations 1
- For Ashkenazi Jewish individuals, initial testing for the three common founder mutations is recommended 1, 3
- If founder mutation testing is negative but other criteria are met, full sequence testing should be considered 1
Pre-Testing Requirements
- Genetic counseling should be provided before testing to discuss 1:
- Benefits, risks, and limitations of genetic testing
- Possible test results and implications for patient and family
- Potential psychological impact
- Cost and insurance considerations
- Privacy and discrimination concerns
Risk Assessment Models
- In some clinical settings, testing decisions may be guided by probability models that estimate the likelihood of identifying a mutation 1:
- BRCAPRO
- BOADICEA
- Manchester Score
- Testing is often considered when there is a 10-20% probability of finding a mutation 1
Important Considerations
- Negative test results in families with strong history but no identified mutation should still be managed with enhanced surveillance, as these individuals still have approximately four-fold increased risk 4
- The risk of breast cancer in mutation carriers has shown a cohort effect, with women born after 1940 having higher risks at younger ages than previous generations 5
- Male breast cancer alone is sufficient criterion for genetic testing regardless of family history 2
- Testing should be performed in adults after obtaining informed consent 1
Post-Testing Management
- Positive results should prompt discussion of risk-reducing strategies and cascade testing of relatives 1
- Variants of uncertain significance should not be used for clinical decision-making 1
- Negative results in families with no known mutation should be managed based on family history risk assessment 1, 4