Outcomes of retesting BRCA negative patients using multigene panels

Area of Science:

• Genetics
• Oncology
• Clinical Diagnostics

Background:

• Multigene panels are increasingly used for hereditary cancer risk assessment.
• The utility of multigene panels for retesting patients with prior negative BRCA1/2 testing is not well-established.
• Previous negative BRCA1/2 testing may not rule out all hereditary cancer predispositions.

Purpose of the Study:

• To evaluate the clinical utility of multigene panel testing in patients with a prior negative BRCA1/2 mutation test.
• To determine the rate of pathogenic mutations identified by multigene panels in this population.
• To assess the impact of multigene panel testing on patient management.

Main Methods:

• Retrospective review of 122 patients tested between November 2012 and June 2015.
• Patients had previously tested negative for BRCA1/2 mutations via standard sequencing.
• Multigene panel testing results and subsequent clinical management changes were analyzed.

Main Results:

• Pathogenic mutations were identified in 13 out of 122 patients (11%).
• Genes with identified mutations included CHEK2, PALB2, ATM, CDH1, APC, BARD1, and MRE11A.
• Clinical management changed for 7 of 11 patients with actionable mutations and 2 patients with mutations in genes lacking clear guidelines.

Conclusions:

• Multigene panel retesting is clinically useful for individuals with prior negative BRCA1/2 results.
• This approach identifies actionable mutations and influences clinical management decisions.
• Panel testing expands the scope of hereditary cancer risk assessment beyond BRCA1/2.