Clinical Actionability of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer Risk Assessment

Area of Science:

• Genetics
• Oncology
• Medical Diagnostics

Background:

• Hereditary breast and/or ovarian cancer (HBOC) genetic testing is evolving with multigene panels.
• Multigene panels identify more mutations than BRCA1/2 testing alone, but their clinical impact is unclear.

Purpose of the Study:

• To determine the clinical effect of multigene panel testing for HBOC in a representative patient cohort.
• To assess the actionability of non-BRCA1/2 mutations identified through panel testing.

Main Methods:

• An observational study of 1046 BRCA1/2-negative HBOC candidates at three academic medical centers (2001-2014).
• Multigene panel testing was performed on all participants.
• Clinical actionability was evaluated based on management guidelines, cancer risks, and patient/family history.

Main Results:

• 3.8% of participants (40/1046) had deleterious non-BRCA1/2 mutations, primarily in moderate-risk genes (CHEK2, ATM, PALB2) and Lynch syndrome genes.
• These mutations were clinically significant, aligning with observed cancer types in patients/families.
• Management changes were considered for 52% of mutation-positive patients, and familial testing for 72% of those with first-degree relatives.

Conclusions:

• Multigene panel testing for HBOC significantly increases the identification of actionable mutations compared to BRCA1/2 testing alone.
• These findings are likely to alter near-term cancer risk assessment and management strategies for a broad range of patients.
• Panel testing provides valuable clinical insights across diverse cancer predisposition genes.