Should a patient with a family history of breast and ovarian cancer in two maternal aunts undergo genetic testing for BRCA1 (Breast Cancer Gene 1) and BRCA2 (Breast Cancer Gene 2) mutations?

Genetic Testing for a Patient with Two Maternal Aunts with Breast and Ovarian Cancer

Yes, your patient should be offered genetic testing based on her family history of two maternal aunts with breast and ovarian cancer, even with unknown BRCA status.

Risk Assessment

The patient's family history represents a significant risk factor that warrants genetic evaluation:

• Having two second-degree relatives (maternal aunts) with breast and ovarian cancer on the same side of the family meets criteria for genetic testing referral according to multiple guidelines 1
• The National Comprehensive Cancer Network (NCCN) guidelines specifically recommend genetic evaluation when there are multiple family members with breast, ovarian, or related cancers 1
• The American College of Medical Genetics and Genomics recommends referral for any individual with a first-degree relative with ovarian cancer or multiple family members with breast or ovarian cancer 1

Benefits of Genetic Testing

Genetic testing in this scenario offers several important benefits:

• Early identification of hereditary cancer risk allows for enhanced screening and risk-reduction strategies
• If a pathogenic mutation is identified, it would significantly impact the patient's medical management including:
  • Earlier and more frequent breast screening
  • Consideration of risk-reducing surgeries
  • Potential chemoprevention options
• Testing would also benefit other family members who could undergo targeted testing if a mutation is found

Testing Approach

1. Initial Genetic Counseling:

   • Discuss the probability of finding a mutation
   • Explain implications for the individual and family
   • Review potential benefits and limitations of testing 1

2. Testing Strategy:

   • Ideally, begin testing with an affected family member (one of the aunts with cancer) if available 1
   • If affected relatives are unavailable for testing, proceed with testing the patient directly 1
   • Test for a comprehensive panel including BRCA1/2 and other hereditary cancer genes

3. Post-Test Management:

   • If positive: Implement high-risk screening and risk-reduction protocols
   • If negative but strong family history remains: Consider enhanced screening based on family history

Important Considerations

• Even if BRCA testing is negative, other genetic mutations may be responsible for the family history of cancer 2
• Studies show that fewer than one-third of early-onset breast cancers in families are related to BRCA1/2 mutations 2
• A negative test result in the setting of strong family history still warrants consideration of increased surveillance

Common Pitfalls to Avoid

• Don't wait for cancer to develop: Proactive genetic testing allows for prevention strategies
• Don't dismiss maternal history: Cancer predisposition genes can be inherited from either parent
• Don't limit testing to BRCA1/2: Consider multi-gene panel testing as other genes may be involved
• Don't underestimate the importance of second-degree relatives: Having multiple affected second-degree relatives significantly increases risk

Genetic testing in this case is strongly supported by current guidelines and has the potential to significantly impact the patient's morbidity, mortality, and quality of life through early identification of cancer risk and implementation of appropriate risk-reduction strategies.