When should a patient be tested for BRCA (Breast Cancer Gene) mutations?

BRCA Testing Recommendations

BRCA genetic testing should be offered to all patients with personal history of breast cancer diagnosed at age ≤45 years, triple-negative breast cancer at age ≤60 years, multiple primary breast cancers, ovarian/fallopian tube/peritoneal cancer, male breast cancer, or those with a significant family history of these cancers, regardless of age. 1, 2

Who Should Be Tested for BRCA Mutations

Personal History Indications

• Patients with breast cancer diagnosed at age ≤45 years 2
• Patients with breast cancer diagnosed at age ≤50 years with one or more close relatives with breast cancer diagnosed at age ≤50 years 2
• Patients with triple-negative breast cancer diagnosed at age ≤60 years 1
• Patients with two primary breast cancers, especially when first diagnosis was before age 50 1, 2
• All patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer 1, 3
• Patients with male breast cancer 1, 2
• Patients with breast cancer at any age with two or more close blood relatives with breast and/or ovarian cancer 2
• Patients with a personal history of both breast and ovarian cancer 1

Family History Indications

• Individuals with a first- or second-degree relative meeting any of the above criteria 2
• Individuals with three or more family members with breast and/or ovarian cancer, with at least one diagnosed before age 50 1
• Individuals with a close male relative with breast cancer 1, 2
• Individuals with a known BRCA1/2 mutation in the family 2

Ethnic Background Considerations

• Ashkenazi Jewish ancestry with personal or family history of breast, ovarian, or pancreatic cancer at any age 1, 2

Timing of Testing

• Genetic testing should ideally be performed at diagnosis of breast or ovarian cancer, though patients can be referred at any stage 1
• Retrospective testing should be offered to patients in long-term follow-up due to implications for family members and future cancer risk 3
• Consideration of screening for BRCA mutations should begin once individuals have reached the age of consent (18 years) 1
• Primary care providers should periodically assess all patients for changes in family history (comprehensive review at least every 5-10 years) 1

Testing Approach

• Initial testing should ideally be performed on an affected family member with the highest likelihood of carrying a mutation 2
• If no affected family member is available, testing may be performed on an unaffected individual, though interpretation of negative results may be more challenging 1, 2
• For individuals of Ashkenazi Jewish descent, testing for the three common founder mutations should be performed first 2
• When multiple genes could explain an inherited cancer syndrome, multigene panel testing is appropriate and may be more cost-effective 4, 2
• Germline BRCA testing of a blood/saliva sample should initially be conducted and, if negative, tumor tissue should be tested to identify somatic BRCA mutations 3

Benefits of BRCA Testing

• Identifies individuals at high risk for developing specific cancers, allowing for enhanced surveillance and early detection 2
• Enables consideration of risk-reducing interventions such as prophylactic mastectomy and/or oophorectomy for mutation carriers 1, 2
• Informs treatment decisions for those already diagnosed with cancer 2
• Provides prognostic information and helps guide management decisions 2

Important Considerations and Potential Pitfalls

• Genetic testing should include pre-test and post-test counseling to discuss risks, benefits, and limitations 1, 2
• A negative test result does not rule out hereditary cancer risk if the family history remains suggestive 4, 2
• Large genomic rearrangements may not be detected by standard sequencing techniques; specific techniques to detect duplications or deletions of exons may be needed 1, 2
• Family history should be periodically reassessed as new cancer events may occur 2
• Primary cancer treatment should not be delayed for genetic counseling referral 2
• The USPSTF recommends against routine genetic counseling for women whose family history is not associated with an increased risk for potentially harmful mutations in the BRCA1/2 genes 1, 5

By following these evidence-based recommendations for BRCA testing, clinicians can identify individuals at high risk for hereditary breast and ovarian cancer syndromes, enabling appropriate risk-reducing interventions that can significantly decrease morbidity and mortality.