01
High-grade ovarian cancer and maintenance therapy
For high-grade tubo-ovarian carcinoma, germline and/or somatic BRCA1/2 testing at diagnosis and HRD evaluation in advanced disease may inform eligibility for PARP-inhibitor maintenance in specified settings. The relevance depends on the regimen and its authorization.
Assay and specimen: Blood or saliva for germline BRCA; validated tumor testing for somatic BRCA and HRD/genomic instability.
Clinical interpretation: HRD positivity does not establish a germline BRCA variant; HRD negativity does not necessarily exclude benefit from all PARP-based regimens.
02
Breast, prostate, and pancreatic cancers
BRCA1/2 results can inform treatment and familial-risk assessment in selected high-risk or metastatic breast cancers, metastatic castration-resistant prostate cancer, and pancreatic cancer. PARP-inhibitor indications vary with tumor type, stage and prior therapy.
Assay and specimen: Appropriate multigene germline testing with pre/post-test counseling; tumor testing tailored to cancer type and treatment line.
Clinical interpretation: A somatic BRCA alteration does not establish hereditary disease. Consider germline testing when clinically indicated.
03
Hereditary risk and cascade testing
A pathogenic or likely pathogenic germline BRCA1/2 variant may change risk reduction and surveillance planning for relatives.
Assay and specimen: Standard variant classification, appropriate copy-number analysis, and targeted family testing after confirming the index variant.
Clinical interpretation: A variant of uncertain significance (VUS) does not justify irreversible prophylactic intervention or pathogenic-variant cascade testing.
