title: Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer.
abstract: Triple-negative breast cancers (TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20 % of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0 years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon-intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6 %) triple-negative patients. The mutation prevalence was 9.3 % in Australia and was 9.9 % in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59 % of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.
authors: School of Biomedical Sciences & Pharmacy, Centre for Information-Based Medicine, Hunter Medical Research Institute, University of Newcastle, Lot 1 Kookaburra Circuit, New Lambton Heights, Newcastle, NSW, 2305, Australia.
authors: Michelle W
authors: MW
authors: Wong-Brown
authors: Cliff J
authors: CJ
authors: Meldrum
authors: Jane E
authors: JE
authors: Carpenter
authors: Christine L
authors: CL
authors: Clarke
authors: Steven A
authors: SA
authors: Narod
authors: Anna
authors: A
authors: Jakubowska
authors: Helena
authors: H
authors: Rudnicka
authors: Jan
authors: J
authors: Lubinski
authors: Rodney J
authors: RJ
authors: Scott
mesh_terms: D000328:Adult; D000368:Aged; D001315:Australia / Q000453:epidemiology; D005091:Exons; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012307:Risk Factors; D064726:Triple Negative Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology