title: Outcomes of retesting BRCA negative patients using multigene panels.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI, 48073, USA. Siddhartha.yadav@beaumont.org.|Nancy and James Grosfeld Cancer Genetics Center, Beaumont Health, 3577 W 13 Mile Rd, Suite 140, Royal Oak, MI, 48073, USA. Siddhartha.yadav@beaumont.org.
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Yadav
authors.affiliation: Nancy and James Grosfeld Cancer Genetics Center, Beaumont Health, 3577 W 13 Mile Rd, Suite 140, Royal Oak, MI, 48073, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Reeves
authors.affiliation: Nancy and James Grosfeld Cancer Genetics Center, Beaumont Health, 3577 W 13 Mile Rd, Suite 140, Royal Oak, MI, 48073, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Campian
authors.affiliation: Nancy and James Grosfeld Cancer Genetics Center, Beaumont Health, 3577 W 13 Mile Rd, Suite 140, Royal Oak, MI, 48073, USA.
authors.forename: Amy
authors.initials: A
authors.lastname: Paine
authors.affiliation: Nancy and James Grosfeld Cancer Genetics Center, Beaumont Health, 3577 W 13 Mile Rd, Suite 140, Royal Oak, MI, 48073, USA.|Oakland University William Beaumont School of Medicine, 2200 N Squirrel Rd, Rochester, MI, 48309, USA.
authors.forename: Dana
authors.initials: D
authors.lastname: Zakalik
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D014408:Biomarkers, Tumor / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D008875:Middle Aged; D012042:Registries; D012189:Retrospective Studies
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor
keywords: Actionability; BRCA negative; Clinical impact; Multigene panel; Outcomes; Retesting