Genomic instability is a hallmark of cancers and mutations in the DNA repair BRCA1 and BRCA2 genes predispose to breast and other cancers. Prevalence of BRCA1/2 mutations is known in general population, but the frequency of these mutations in patients with metastatic breast cancer has not been established.
Prospective BRCA1 and BRCA2 genetic testing was proposed to all patients with metastatic breast cancer treated in 7 centers (in Franche-Comte, France) between February 19th 2015 and November 30th. BRCA TrueTM test (Pathway Genomics®, San Diego CA, USA) was used to analyze the coding and flanking regions of BRCA1 and BRCA2 genes associated with hereditary breast and ovarian cancer by next-generation sequencing-base and Sanger sequencing.
Of the 407 metastatic breast cancer patients, 11 (2.7%) had pathogenic germline BRCA1/2 mutations. BRCA2 (n = 8) mutations were the most frequent. Five of 11 patients (45%) would not have been candidate for BRCA1/2 mutation screening according to genetic counseling recommendations. All patients with a BRCA2 mutation presented a luminal metastatic breast cancer whereas all patients with BRCA1 mutation had a triple-negative metastatic breast cancer.
This is the first study assessing the prevalence of germline BRCA1 and BRCA2 mutations in an unselected population of patients with metastatic breast cancer. These patients with BRCA1/2 germline mutation represent the targeted population for poly(ADP-ribose) polymerase (PARP) inhibitors based therapy.
Clinical trial identification
Legal entity responsible for the study
University Hospital Jean Minjoz of Besancon, France
All authors have declared no conflicts of interest.