Should I order BRCA (Breast Cancer Gene) testing for a patient with a significant family history of breast cancer?

BRCA Testing for Patients with Family History of Breast Cancer

BRCA testing should be ordered for patients with a significant family history of breast cancer, following appropriate risk assessment and genetic counseling. 1, 2

Risk Assessment and Criteria for Testing

Family History Factors That Warrant BRCA Testing:

• Breast cancer diagnosis in a family member before age 50 years
• Bilateral breast cancer in a family member
• Both breast and ovarian cancer in the same individual or family
• Male breast cancer in the family
• Multiple cases of breast cancer in the family
• One or more family members with two primary types of BRCA-related cancer
• Ashkenazi Jewish ancestry with breast or pancreatic cancer at any age
• Triple-negative breast cancer diagnosed at age ≤60 years

Risk Assessment Tools:

Several validated screening tools can help determine if genetic testing is appropriate:

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

The Referral Screening Tool and FHS-7 are the quickest to administer, with most tools having sensitivity estimates >85% for identifying appropriate candidates for genetic counseling 1.

Testing Protocol

1. First Step: Risk Assessment

   • Collect detailed family history of cancer on both maternal and paternal sides
   • Include information about cancer type, age at diagnosis, and affected relatives
   • Apply a validated risk assessment tool

2. Second Step: Genetic Counseling

   • Should be performed by trained health professionals
   • Includes detailed kindred analysis and risk assessment
   • Educates about possible test results and implications
   • Identifies affected family members who may be preferred candidates for testing

3. Third Step: Testing Strategy

   • When possible, begin testing with an affected family member (preferred approach) 1
   • If no affected relative is available, testing the unaffected individual is reasonable 1
   • For Ashkenazi Jewish individuals, test for the three common founder mutations first 1
   • For non-Ashkenazi Jewish individuals with no known familial mutation, full sequence testing is recommended 1

Implications of Test Results

Positive Results (Mutation Detected):

• Women with BRCA1 mutations have 65-80% lifetime risk of breast cancer and 37-62% risk of ovarian cancer
• Women with BRCA2 mutations have 45-85% lifetime risk of breast cancer and 11-23% risk of ovarian cancer 1
• Management includes:
  • Breast self-exam training starting at age 18
  • Clinical breast exams every 6 months starting at age 25
  • Annual mammogram and breast MRI screening starting at age 25-30 1, 2
  • Consider risk-reducing mastectomy and salpingo-oophorectomy 1

Negative Results:

• True negative (when a family mutation is known): Generally not at increased risk 1
• Uninformative negative (when no family mutation is identified): Continue screening based on family history

Common Pitfalls to Avoid

1. Using general breast cancer risk models: Do not use general breast cancer risk assessment models (like the Gail model) to determine need for BRCA testing 1

2. Limited family history collection: Family structure with fewer than 2 first- or second-degree female relatives or female relatives surviving beyond age 45 may underestimate mutation probability 1

3. Ignoring paternal family history: BRCA mutations can be inherited from either parent 2

4. Delaying testing due to treatment: Genetic counseling referral should not delay primary treatment and can be arranged concurrently with treatment planning 2

5. Overlooking anticipation phenomenon: Research suggests BRCA-related cancers may be diagnosed at earlier ages in subsequent generations, which may impact screening recommendations 3

By following these guidelines, you can appropriately identify patients who would benefit from BRCA testing and provide them with the necessary management to reduce their risk of developing breast and ovarian cancer.