What is the recommendation for approved BRCA (Breast Cancer Gene) testing?

BRCA Testing Recommendations

Women with a personal or family history of breast, ovarian, tubal, or peritoneal cancer, or those with Ashkenazi Jewish ancestry, should undergo risk assessment using a validated familial risk tool, followed by genetic counseling and BRCA testing if the tool indicates increased risk. Routine BRCA testing should not be performed in women without such risk factors. 1, 2

Risk Assessment and Screening Approach

Who Should Be Assessed for BRCA Testing

Primary care clinicians must screen all women for:

• Personal history of breast cancer diagnosed ≤45 years 3
• Personal history of breast cancer diagnosed ≤50 years with one or more close blood relatives with breast cancer 3
• Triple-negative breast cancer diagnosed before age 50 3
• Epithelial ovarian, fallopian tube, or primary peritoneal cancer at any age 3, 4
• Male breast cancer (regardless of family history) 5, 3
• Two primary breast cancers, especially if first diagnosis occurred before age 50 3
• Ashkenazi Jewish descent with breast cancer diagnosed before age 60 3

Family history red flags requiring assessment:

• Three or more breast and/or ovarian cancers on the same side of the family, with at least one diagnosed before age 50 3
• Two breast cancers in close relatives diagnosed before age 40 3
• First- or second-degree blood relative meeting any of the above personal history criteria 3
• Known mutation in a breast cancer susceptibility gene in a family member 3

Risk Assessment Tools for Primary Care

The USPSTF found several validated brief familial risk stratification tools suitable for primary care use, though no single tool is superior 1. The simplest and quickest tools are:

• Referral Screening Tool (B-RST): Available at www.breastcancergenescreen.org 1
• Family History Screen-7 (FHS-7) 1

Other validated tools include the Ontario Family History Assessment Tool, Manchester Scoring System, and Pedigree Assessment Tool, all with sensitivity estimates >85% 1.

Critical caveat: Do NOT use general breast cancer risk assessment models like the Gail model, as these are not designed to determine who needs genetic counseling or BRCA testing 1.

Genetic Counseling Requirements

Pre-Test Counseling (Mandatory)

All women must receive genetic counseling before testing that addresses: 1, 3

• Benefits, risks, and limitations of genetic testing 3
• Possible test results and implications for the patient and family 3
• Potential psychological impact 3
• Cost and insurance considerations 3
• Privacy and discrimination concerns 3

Post-Test Counseling

Because of the complexity of BRCA test results, the USPSTF recommends posttest counseling 1. This is particularly important given that variants of uncertain significance should not be used for clinical decision-making 3.

Testing Strategy

Optimal Testing Sequence

The preferred BRCA testing strategy is initial testing of an affected family member with breast or ovarian cancer 1, 3. However, it is reasonable to start testing in an unaffected individual if no affected relative is available 1.

Special Population Considerations

For Ashkenazi Jewish individuals:

• Initial testing for the three common founder mutations is recommended 3
• If founder mutation testing is negative but other criteria are met, full sequence testing should be considered 3

For ovarian cancer patients:

• All patients with invasive epithelial ovarian cancer (excluding borderline or mucinous), including fallopian tube and peritoneal cancers, should be considered for BRCA testing regardless of age 4
• Testing should ideally be offered at diagnosis, though patients can be referred at any stage 4
• Germline BRCA testing of blood/saliva should initially be conducted; if negative, tumor tissue should be tested to identify somatic BRCA mutations 4

For male breast cancer:

• Male breast cancer alone is a criterion for genetic testing, regardless of family history 5
• BRCA2 mutations are particularly common, with carriers having a 6-7% lifetime risk of breast cancer 5

Who Should NOT Receive Routine Testing

The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing for women whose personal or family history or ancestry is not associated with potentially harmful BRCA1/2 gene mutations (D recommendation). 2 For these women, the net benefit ranges from minimal to potentially harmful 1.

Clinical Benefits and Harms

Benefits of Testing

For women with increased risk based on family history, the net benefit of testing, detection, and early intervention is moderate 1. Benefits include:

• Access to intensive cancer screening 2
• Risk-reducing medications 2
• Risk-reducing surgery options 2
• Cascade testing of relatives to identify at-risk individuals 5, 3

For male BRCA2 carriers, identification has implications for increased risk of prostate (5-25%), pancreatic (up to 2%), and stomach cancers 5.

Harms of Testing

The overall harms of testing, detection, and early intervention are small to moderate 1, 2. These include potential psychological effects and risks associated with risk-reducing interventions 1.

Common Pitfalls to Avoid

• Do not use general breast cancer risk models (like Gail model) to determine who needs BRCA testing 1
• Do not skip genetic counseling before or after testing 1
• Do not test unaffected individuals first when affected family members are available 1, 3
• Do not use variants of uncertain significance for clinical decision-making 3
• Do not limit testing to those with strong family history in specific populations (e.g., all women with high-grade serous ovarian carcinoma should be tested) 4, 6