What are the initial steps for risk stratification in a patient with a family history of BRCA (Breast Cancer Gene)?

Risk Stratification for Patients with Family History of BRCA Mutations

The initial step for risk stratification in a patient with a family history of BRCA mutations should be obtaining a detailed three-generation pedigree that includes first-, second-, and third-degree relatives on both maternal and paternal sides of the family. 1

Comprehensive Family History Assessment

Essential Components:

• Document cancer history for all first-, second-, and third-degree relatives including:
  • Type of cancer
  • Age at diagnosis
  • Bilateral disease (if applicable)
  • Multiple primary cancers in the same individual
  • Death from cancer and age at death
  • Ethnicity (particularly Ashkenazi Jewish descent)

Red Flags in Family History:

• Early-onset breast cancer (diagnosed before age 50) 1
• Multiple affected relatives with breast and/or ovarian cancer
• Male breast cancer
• Triple-negative breast cancer
• Ovarian, fallopian tube, or primary peritoneal cancer
• Bilateral breast cancer
• Pancreatic cancer or prostate cancer (especially if early-onset)
• Known BRCA mutation in the family

Risk Assessment Tools

After collecting a detailed family history, the next step is to use specialized risk assessment models to estimate:

1. Lifetime risk of developing breast/ovarian cancer
2. Probability of carrying a BRCA mutation

Recommended Risk Assessment Models:

• BRCAPRO - evaluates likelihood of BRCA1/2 mutation 1
• BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) - estimates both cancer risk and mutation probability 1
• Tyrer-Cusick model - evaluates breast cancer risk 1
• Claus model - useful for white women with 1-2 first or second-degree relatives with breast cancer 1

Note: The Gail model is NOT appropriate for hereditary risk assessment as it cannot analyze detailed family histories including first and second-degree relatives on both maternal and paternal sides 1.

Criteria for Genetic Counseling Referral

Refer for genetic counseling if any of the following criteria are met:

Personal History Criteria:

• Breast cancer diagnosed ≤45 years
• Breast cancer diagnosed ≤50 years with ≥1 close relative with breast cancer at any age
• Triple-negative breast cancer diagnosed ≤60 years
• Two breast primaries when first diagnosis occurred before age 50
• Ovarian/fallopian tube/primary peritoneal cancer at any age
• Male breast cancer at any age

Family History Criteria:

• ≥1 first-degree relative meeting any of the above criteria
• ≥2 close blood relatives with breast cancer, with at least one diagnosed ≤50 years
• ≥3 close blood relatives with breast cancer at any age
• A known mutation in a breast cancer susceptibility gene in the family
• First or second-degree relative with breast cancer ≤50 years
• Two or more relatives with breast and/or ovarian cancer
• A family member with both breast and ovarian cancer

Next Steps After Risk Assessment

For High-Risk Individuals (≥20% lifetime risk or BRCA mutation carrier):

• Refer for genetic counseling and potential genetic testing
• Consider enhanced screening protocols:
  • Annual mammography starting at age 30
  • Annual breast MRI starting at age 30 (for confirmed BRCA carriers or those with ≥20-25% lifetime risk) 1
  • Risk-reducing medication options discussion
  • Discussion of risk-reducing surgical options

For Moderate-Risk Individuals:

• Individualized screening recommendations based on specific risk factors
• Consider more frequent clinical breast examinations
• Consider earlier initiation of mammography screening

For Average-Risk Individuals:

• Standard population screening guidelines
• Breast awareness education

Important Considerations

• Both maternal and paternal family histories are equally important 1
• Limited family structure (few female relatives or early deaths) may lead to underestimation of genetic risk 1
• Verification of cancer diagnoses through medical records is important when possible 1, 2
• Self-reported family histories are generally accurate for first-degree relatives but less reliable for second-degree relatives 2
• Extended family history (beyond first-degree relatives) significantly improves identification of high-risk individuals 3

Remember that a cancer geneticist or genetic counselor should be involved early in the process for patients who potentially meet criteria for an inherited cancer syndrome 1.