BRCA Testing in Breast Cancer: Germline vs. Tissue
BRCA testing in breast cancer is performed on germline (blood or saliva) samples, not tumor tissue. The 2024 ASCO-SSO guidelines explicitly focus on "germline genetic testing" and "germline pathogenic variants" throughout all recommendations 1.
Why Germline Testing is Standard
Germline testing identifies inherited mutations that are present in all cells of the body and can be passed to offspring, which is the primary clinical objective for BRCA testing in breast cancer patients 2, 3.
Key Clinical Implications of Germline Testing:
Treatment decisions: Germline BRCA1/2 mutations determine eligibility for PARP inhibitor therapy (olaparib, talazoparib) in both early-stage and metastatic breast cancer 1, 2, 4
Surgical planning: Germline carriers face significantly elevated risks of contralateral breast cancer, informing decisions about bilateral mastectomy versus breast-conserving surgery 5
Risk-reducing strategies: Germline results guide recommendations for risk-reducing salpingo-oophorectomy to manage ovarian cancer risk 5
Family cascade testing: Identifying germline variants enables at-risk relatives to pursue appropriate surveillance and risk-reduction strategies before cancer develops 5
Practical Testing Approach
Blood or saliva samples are collected for DNA extraction and analyzed using next-generation sequencing-based multi-gene panels 6.
Testing is performed on peripheral blood samples, not tumor tissue 6, 7
Multi-gene panels typically include BRCA1/2 plus other high-penetrance genes (PALB2, TP53, PTEN, STK11, CDH1) based on personal and family history 2, 6
Important Distinction: Germline vs. Somatic Testing
While somatic (tumor) testing exists and can identify BRCA mutations acquired only in the tumor, this is fundamentally different from germline testing 8.
Somatic mutations are not inherited and cannot be passed to offspring 8
Somatic BRCA mutations may still predict PARP inhibitor sensitivity, but do not inform family risk 8
Paired testing (both germline and somatic) can be performed, but the standard approach for hereditary cancer assessment is germline testing 8
Common Pitfall to Avoid:
Do not confuse tumor molecular profiling with germline genetic testing. Tumor sequencing identifies somatic mutations to guide targeted therapy for that specific cancer, while germline testing identifies inherited mutations with implications for the patient's lifetime cancer risk and family members 8, 4.