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Abstract
Multigene panel tests are being increasingly used for the genetic assessment of women with an apparent predisposition to breast cancer. Here, we review all studies reporting results from individuals who have undergone multigene panel testing for hereditary breast cancer. Across all gene panel studies, the prevalence of pathogenic mutations was highest in BRCA1 (5.3%) and BRCA2 (3.6%) and was lowest in PTEN (0.1%), CDH1 (0.1%) and STK11 (0.01%). After BRCA1/2, the prevalence of pathogenic mutations was highest in CHEK2 (1.3%), PALB2 (0.9%) and ATM (0.8%). The prevalence of variants of unknown significance was highest in ATM (9.6%). Based on the prevalence and penetrance of pathogenic mutations and the prevalence of variants of unknown significance, it is our interpretation that BRCA1, BRCA2, PALB2 and CHEK2 are the best candidates for inclusion in a clinical multigene breast cancer panel.
Financial & competing interests disclosure
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.
No writing assistance was utilized in the production of this manuscript.
With advances in sequencing technology, multigene panel tests are increasingly being used for the genetic assessment of women with an apparent predisposition to breast cancer; however, the clinical utility of these gene panels has not yet been established.
We conducted a review of all studies reporting results from individuals who underwent multigene panel testing for hereditary breast cancer in order to evaluate the clinical utility of breast cancer gene panels.
Across all gene panel studies, the prevalence of pathogenic mutations was highest in BRCA1 (5.3%) and BRCA2 (3.6%) and was lowest in PTEN (0.1%), CDH1 (0.1%) and STK11 (0.01%).
After BRCA1/2, the prevalence of pathogenic mutations was highest in CHEK2 (1.3%), PALB2 (0.9%) and ATM (0.8%).
The prevalence of VUS was highest in ATM (9.6%).
BRCA1, BRCA2, TP53, CDH1, PTEN, STK11, PALB2 and CHEK2 are all associated with lifetime risks for breast cancer in excess of 25% (i.e., the cutoff for annual MRI screening) and therefore genetic testing for mutations in these genes is expected to influence the clinical management of breast cancer.
Based on the prevalence and penetrance of pathogenic mutations and the prevalence of VUS, it is our interpretation that BRCA1, BRCA2, CHEK2 and PALB2 are the best candidates for inclusion in a clinical genetic testing panel.