Background The practice of genetic testing is rapidly evolving with the recent introduction of multi-gene panels. While the prevalence of non-BRCA1/2 mutations in HBOC patients is now well documented, the clinical impact of these findings is not yet fully understood.
Objectives We sought to measure how often and in which ways non-BRCA1/2 findings might change patient management recommendations in a representative clinical cohort.
Design/method We used similar 25 or 29 gene panels to test over 1000 BRCA1/2-negative patients, all of whom were enrolled prospectively at three academic medical centres and all met NCCN guidelines for HBOC evaluation. We established a uniform algorithm based on current practice guidelines to recommend management actions for the non-BRCA1/2 positive individuals, and we evaluated which of these recommendations would represent changes in management above and beyond any recommendations based on personal and family history alone.
Results 63 patients were identified with pathogenic or likely pathogenic mutations in non-BRCA1/2 genes. We found that the majority of these findings (52%) would result in consideration of additional screening and/or prevention measures for the patient. Moreover, we found that genetic testing of 70% of first-degree family members would also be warranted given the potential management changes in these individuals if found to be mutation positive.
Conclusions In appropriately referred patients, multi-gene panel testing yields clinically relevant findings with potential management impact for more patients than does BRCA1/2 testing alone.
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