#Grand Rounds

Single Gene vs Multigene Panel Testing for Cancer Predisposition: Are Guidelines Too Restrictive?

BACKGROUND AND PURPOSE:

Multigene panel testing (MGPT) for hereditary cancer predisposition is becoming increasingly available
- MGPT includes additional genes that may be important for a particular cancer (e.g., other genes beyond BRCA1/2 for breast cancer)
- MGPT can be helpful for heritable syndromes that include multiple cancers
Evidence-based guidelines often suggest starting with smaller genetic panels depending on the clinical scenario
DaLuca et al. (Genetics in Medicine, 2019) sought to compare MGPT to the more traditional targeted gene panels recommended by NCCN for BRCA-related breast and/or ovarian cancer syndrome and Lynch syndrome

Retrospective review
Participants
- Patients undergoing hereditary cancer predisposition testing with MGPT
- Cancer Indications: Breast | Ovarian | Colorectal | Uterine/endometrial | Pancreatic | Pan-cancer
32 cancer predisposition genes

Pathogenic variant frequencies
- Highest among patients with ovarian cancer (13.8%) | Lowest among patients with melanoma (8.1%)
Using NCCN guidelines, the majority of pathogenic variants would be missed
- BRCA1/2 testing guidelines: Only 33.1% of pathogenic variants would be detected using targeted panels
- Lynch syndrome guidelines: Only 46.2% of pathogenic variants would be detected using the targeted Lynch syndrome panels
Using NCCN guidelines, some women with pathogenic variants would not have met criteria for testing
- Breast cancer: 5.8% of patients with pathogenic variants in BRCA1/2 would be missed
- Lynch syndrome: 26.9% of patients with pathogenic variants in Lynch syndrome genes would be missed

More at-risk patients would be identified
- Using multigene panel testing rather than limited panels specific to a particular cancer syndrome
- If NCCN guidelines were less restrictive (e.g., lowering age at diagnosis constraints)

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