Frequent incidence of BARD1-truncating mutations in germline DNA from triple-negative breast cancer patients

Area of Science:

• Oncology
• Genetics
• Cancer Research

Background:

• Triple-negative breast cancer (TNBC) represents 10-20% of all breast cancers (BCs).
• Conventional chemotherapy is the primary systemic treatment for TNBC.
• Germline BRCA1/2 mutations occur in about 15% of TNBC patients.

Purpose of the Study:

• To investigate the frequency of germline mutations in BRCA1, BRCA2, and BARD1 genes in TNBC patients.
• To assess the potential role of BARD1 mutations in TNBC susceptibility.
• To identify TNBC patients eligible for targeted therapies like PARP inhibitors.

Main Methods:

• Germline DNA analysis was performed on 61 estrogen receptor-negative patients, including 42 with TNBC.
• Mutational analysis focused on BRCA1, BRCA2, and BARD1 genes.
• Comparison of mutation frequencies in TNBC patients versus control and high-risk BC families.

Main Results:

• BRCA1/2 mutations were identified in 19% (8/42) of TNBC patients, but not in the ER-/HER2+ cohort.
• Four candidate pathogenic BARD1 mutations, including two protein-truncating variants, were found in the TNBC cohort.
• TNBC patients showed enrichment for pathogenic BARD1 germline mutations compared to controls.

Conclusions:

• TNBC patients exhibit an increased prevalence of pathogenic BARD1 germline mutations.
• A significant proportion of TNBC patients (10/42) harbor BRCA pathway mutations (BRCA1, BRCA2, or BARD1).
• These findings suggest that TNBC patients with BRCA pathway mutations may benefit from poly (ADP-ribose) polymerase (PARP) inhibitors.