Genetic testing should be performed in a setting that has suitably trained health care providers who can give appropriate pre- and post-test counseling and that has access to a Clinical Laboratory Improvement Amendments-licensed laboratory that offers comprehensive variant analysis (see Policy Guidelines section: Comprehensive Variant Analysis).
Individuals With Cancer or With a Personal History of Cancer
Genetic testing for BRCA1, BRCA2, and PALB2 variants in cancer-affected individuals may be considered medically necessary under any of the following circumstances:
Individuals with any close blood relative with a known BRCA1, BRCA2, or PALB2 pathogenic/likely pathogenic variant (see Policy Guidelines for definitions and for testing strategy).
Individuals meeting the criteria below but with previous limited testing (eg, single gene and/or absent deletion duplication analysis)
Personal history of breast cancer and 1 or more of the following:
Diagnosed at age ≤45 years; or
Diagnosed 46 to 50 years with:
An additional breast cancer primary at any age; or
≥1 close relative (see Policy Guidelines) with breast, ovarian, pancreatic, or prostate cancer at any age; or
An unknown or limited family history
Diagnosed ≤60 years with:
Triple-negative breast cancer (see Policy Guidelines)
Diagnosed at any age with:
≥1 close blood relative with:
Breast cancer diagnosed ≤50 years; or
Ovarian carcinoma; or
Metastatic or intraductal/cribriform prostate cancer, or high-risk group or very-high-risk group (see Policy Guidelines) prostate cancer; or
Pancreatic cancer; or
≥ 3 total diagnoses of breast cancer in individual and/or close blood relatives; or
Ashkenazi Jewish ancestry
Diagnosed at any age with male breast cancer
Personal history of epithelial ovarian carcinoma (including fallopian tube cancer or peritoneal cancer) at any age
Personal history of exocrine pancreatic cancer at any age
Personal history of metastatic or intraductal/cribriform histology prostate cancer at any age; or high-risk group or very-high-risk group prostate cancer at any age
Personal history of prostate cancer at any age with:
≥1 close blood relative with ovarian carcinoma, pancreatic cancer, or metastatic or intraductal/cribriform prostate cancer at any age, or breast cancer ≤50 years; or
≥2 close blood relatives with breast or prostate cancer (any grade) at any age; or
Ashkenazi Jewish ancestry
Personal history of cancer and a mutation identified on tumor genomic testing that has clinical implications if also identified in the germline.
Individuals Without Cancer or With Other Personal History of Cancer
(See Policy Guidelines section: Testing Unaffected Individuals.)
Genetic testing for BRCA1, BRCA2, and PALB2 variants of cancer-unaffected individuals and individuals with cancer but not meeting the above criteria (including individuals with cancers unrelated to hereditary breast ovarian cancer syndrome) may be considered medically necessary under any of the following circumstances:
An individual with or without cancer and not meeting the above criteria but who has a 1st- or 2nd-degree blood relative meeting any criterion listed above for Patients With Cancer (except individuals who meet criteria only for systemic therapy decision-making). If the individual with cancer has pancreatic cancer or prostate cancer (metastatic or intraductal/cribriform or high-risk group or very-high-risk group) then only first-degree relatives should be offered testing unless there are other family history indications for testing.
An individual with any type of cancer (cancer related to hereditary breast ovarian cancer syndrome but not meeting above criteria, or cancer unrelated to hereditary breast ovarian cancer syndrome) or unaffected individual who otherwise does not meet the criteria above but has a probability >5% of a BRCA1/2 or PALB2 pathogenic variant based on prior probability models (eg, Tyrer-Cuzick, BRCAPro, Pennll).
Genetic testing for BRCA1 and BRCA2 variants of cancer-affected individuals or cancer-unaffected individuals with a family history of cancer when criteria above are not met is considered investigational.
Testing for PALB2 variants in individuals who do not meet the criteria outlined above is considered investigational.
Genetic testing in minors for BRCA1, BRCA2, and PALB2 variants for hereditary breast ovarian cancer syndrome is considered investigational (see Policy Guidelines).
