Outcomes of retesting BRCA negative patients using multigene panels

The utility of multigene panels in retesting patients who previously tested negative for a pathogenic mutation by BRCA1/2 testing is not well established. Patients who previously tested negative for a pathogenic BRCA1/2 mutation by standard sequencing, and who were seen in cancer genetics center between November 1, 2012 and June 30, 2015 for additional testing utilizing multigene panels, were identified using our genetic testing registry. Data on demographics, personal and family history of cancer, results of panel testing and the impact on patient management was collected retrospectively. A total of 122 patients underwent retesting during the study period. Thirteen (11%) pathogenic mutations were identified in the following genes: CHEK2(4), PALB2(3), ATM(2), CDH1, APC, BARD1 and MRE11A. Eleven out of these thirteen mutations were deemed actionable based on published guidelines. Of these eleven, seven patients had an actual change in clinical management as a result of retesting. Furthermore, retesting also led to a change in clinical management in the two patients with mutations in genes (BARD1 and MRE11A) which do not have clear guidelines for management. There were no significant differences in demographics and personal and family history of cancer between patients who tested positive and those who tested negative on retesting. This study demonstrates the clinical utility of multigene panels in a group of high risk individuals who previously tested negative for a BRCA1/2 mutation. This retesting approach revealed a pathogenic mutation in 11% of cases. Retesting led to significant change in clinical management in a majority of patients with actionable mutations (7 out of 11), as well as in those with mutations in genes which do not have specific management guidelines.