title: Frequent incidence of BARD1-truncating mutations in germline DNA from triple-negative breast cancer patients.
abstract: Triple-negative breast cancer (TNBC) accounts for 10-20% of all breast cancers (BCs), and conventional chemotherapy is the only effective systemic treatment. Germline BRCA1/2 mutations are found in approximately 15% of TNBC patients. In the past, we have documented pathogenic mutations in BARD1, a BRCA1 interacting protein, in families at high risk for BC. In this study, we have analyzed germline DNA from 61 estrogen receptor negative patients (of which 42 were TNBC) for the presence of mutations in the BRCA1, BRCA2 and BARD1 gene. BRCA1/2 mutations were found in 8 out of 42 (19%) TNBC patients, but not in the ER-/HER2+ cohort. We also found four good candidate pathogenic BARD1 mutations in the TNBC cohort, including two protein-truncating mutations (p.Gln564Ter and p.Arg641Ter). Our data suggest that TNBC patients are enriched for pathogenic BARD1 germline mutations as compared to control samples and high BC risk families. Ten of the 42 investigated TNBC patients carry a BRCA pathway mutation (in BRCA1, BRCA2 or BARD1) rendering them susceptible to homologous recombination deficiency. These patients should become eligible for exploring the efficacy of poly (ADP-ribose) polymerase (PARP) inhibitors.
authors.affiliation: Laboratory of Molecular and Medical Oncology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: De Brakeleer
authors.affiliation: Department of Medical Oncology, Oncologisch Centrum, Brussels, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: De Grève
authors.affiliation: Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Jules Bordet Institute, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Desmedt
authors.affiliation: Department of Medical Oncology, Oncologisch Centrum, Brussels, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Joris
authors.affiliation: Breast Cancer Translational Research Laboratory, Université Libre de Bruxelles, Jules Bordet Institute, Brussels, Belgium.
authors.forename: C
authors.initials: C
authors.lastname: Sotiriou
authors.affiliation: Department of Medical Oncology, Jules Bordet Institute, Brussels, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Piccart
authors.affiliation: Department of Medical Oncology, Oncologisch Centrum, Brussels, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Pauwels
authors.affiliation: Laboratory of Molecular and Medical Oncology, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: E
authors.initials: E
authors.lastname: Teugels
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D059765:Homologous Recombination; D006801:Humans; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases
keywords: BARD1; BRCA1; BRCA2; PARP inhibitor; germline mutation; triple-negative breast cancer