What is the role of genetic testing for breast cancer in individuals with a strong family history of the disease?

Genetic Testing for Breast Cancer in Individuals with Strong Family History

Genetic testing should be offered to individuals with a strong family history of breast cancer, as it can identify those with BRCA1/2 mutations who would benefit from enhanced surveillance and risk-reduction strategies. 1

Risk Assessment and Referral Criteria

Primary care providers should use structured risk assessment tools to identify candidates for genetic counseling:

• Family history indicators warranting referral:

  • Breast cancer diagnosis before age 50
  • Bilateral breast cancer
  • Both breast and ovarian cancer in one individual
  • Male breast cancer
  • Multiple cases of breast cancer in the family
  • Ashkenazi Jewish ancestry
  • One or more family members with two primary types of BRCA-related cancer 1

• Validated risk assessment tools:

  • Ontario Family History Assessment Tool
  • Manchester Scoring System
  • Referral Screening Tool (B-RST)
  • Pedigree Assessment Tool
  • Family History Screen-7 (FHS-7) 1

Note: General breast cancer risk assessment models (e.g., Gail model) should NOT be used to determine need for genetic testing as they aren't designed for this purpose 1

Genetic Testing Process

Pre-Test Genetic Counseling

Before testing, patients should receive counseling that includes:

• Detailed family history analysis
• Risk assessment for BRCA mutations
• Education about possible test results and implications
• Discussion of screening and risk-reduction options 1

Testing Strategy

1. First-line approach: Test an affected family member with breast/ovarian cancer first 1
2. If no affected relative is available: Testing can begin with the unaffected individual, but limitations of interpretation should be discussed 1
3. For Ashkenazi Jewish individuals: Initial testing for the three founder mutations, followed by full sequencing if negative but family history remains concerning 1

Types of Results and Their Interpretation

• Positive: Pathogenic mutation detected
• Variant of Uncertain Significance (VUS): Genetic change with unclear clinical significance
• True negative: No mutation found in someone whose family has a known mutation
• Uninformative negative: No mutation found, but family mutation status unknown 1

Management Based on Test Results

For BRCA1/2 Mutation Carriers

Women:

• Monthly breast self-exams starting at age 18
• Semi-annual clinical breast exams starting at age 25
• Annual mammogram and breast MRI starting at age 25 (or individualized based on earliest onset in family)
• Consider risk-reducing mastectomy based on individual circumstances
• Recommend risk-reducing salpingo-oophorectomy between ages 35-40 after childbearing
• Consider chemoprevention options 1

Men:

• Monthly breast self-exams
• Regular prostate cancer screening 1

For Those with Negative Results

• True negative: Generally follow population screening guidelines, as breast cancer risk is not significantly increased 2
• Uninformative negative: Higher risk than general population; management should be based on family history 1

Important Considerations and Pitfalls

• VUS results: Should not be used for clinical decision-making; patients should be managed based on family history 1
• Limited sensitivity: Current testing may miss some mutations; a negative result doesn't exclude hereditary risk 1
• Psychological impact: Rapid genetic testing can cause distress but most patients find the information valuable for decision-making 3
• Evolving field: Gene panels now test for multiple genes beyond BRCA1/2, including moderate-risk genes like ATM and CHEK2 4

Genetic testing for breast cancer susceptibility has evolved significantly since the discovery of BRCA1/2. While these genes account for approximately 20-30% of hereditary breast cancer, newer panel testing can identify additional genetic factors contributing to risk 4. The benefits of testing include enabling enhanced surveillance and risk-reduction strategies for mutation carriers, while avoiding unnecessary interventions for non-carriers.

AI: I need to revise my recommendation to be more definitive and focus on the highest quality evidence.