Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer
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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.
KeywordsTriple-negative breast cancer BRCA1 BRCA2 Germline mutations Prevalence Genetic testing
List of abbreviations
Breast cancer susceptibility gene
Poly (adenosine diphosphate)-ribose polymerase
Triple-negative breast cancer
Pathological complete response
DNA samples were received from the Australian Breast Cancer Tissue Bank, which is generously supported by the National Health and Medical Research Council of Australia (NHMRC), the Cancer Institute NSW (CINSW) and the National Breast Cancer Foundation (NBCF). The tissues and samples are made available to researchers on a non-exclusive basis. This work was supported by the National Breast Cancer Foundation (NBCF), Australia. Dr Michelle Wong-Brown is supported by the Hunter Translational Cancer Research Centre with funding from the Cancer Institute New South Wales.
Conflict of interest
The authors of this article declare no competing interests related to the study and no commercial associations that may pose a conflict of interest.
- 3.Gonzalez-Angulo AM, Timms KM, Liu S, Chen H, Litton JK, Potter J, Lanchbury JS, Stemke-Hale K, Hennessy BT, Arun BK et al (2011) Incidence and outcome of BRCA mutations in unselected patients with triple receptor-negative breast cancer. Clin Cancer Res 17(5):1082–1089CrossRefPubMedCentralPubMedGoogle Scholar
- 4.Lakhani SR, Van De Vijver MJ, Jacquemier J, Anderson TJ, Osin PP, McGuffog L, Easton DF (2002) The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, HER-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20(9):2310–2318CrossRefPubMedGoogle Scholar
- 9.Fostira F, Tsitlaidou M, Papadimitriou C, Pertesi M, Timotheadou E, Stavropoulou AV, Glentis S, Bournakis E, Bobos M, Pectasides D et al (2012) Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study. Breast Cancer Res Treat 134(1):353–362CrossRefPubMedGoogle Scholar
- 10.Robertson L, Hanson H, Seal S, Warren-Perry M, Hughes D, Howell I, Turnbull C, Houlston R, Shanley S, Butler S et al (2012) BRCA1 testing should be offered to individuals with triple-negative breast cancer diagnosed below 50 years. Br J Cancer 106(6):1234–1238CrossRefPubMedCentralPubMedGoogle Scholar
- 12.Phuah SY, Looi LM, Hassan N, Rhodes A, Dean S, Taib NA, Yip CH, Teo SH (2012) Triple-negative breast cancer and PTEN (phosphatase and tensin homologue) loss are predictors of BRCA1 germline mutations in women with early-onset and familial breast cancer, but not in women with isolated late-onset breast cancer. Breast Cancer Res 14(6):R142CrossRefPubMedCentralPubMedGoogle Scholar
- 13.An open access on-line breast cancer mutation data base [http://research.nhgri.nih.gov/bic/]
- 14.Borg A, Haile RW, Malone KE, Capanu M, Diep A, Torngren T, Teraoka S, Begg CB, Thomas DC, Concannon P et al (2010) Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study. Hum Mutat 31(3):E1200–E1240CrossRefPubMedCentralPubMedGoogle Scholar
- 16.Bayraktar S, Gutierrez-Barrera AM, Liu D, Tasbas T, Akar U, Litton JK, Lin E, Albarracin CT, Meric-Bernstam F, Gonzalez-Angulo AM et al (2011) Outcome of triple-negative breast cancer in patients with or without deleterious BRCA mutations. Breast Cancer Res Treat 130(1):145–153CrossRefPubMedCentralPubMedGoogle Scholar
- 17.NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) [www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf]
- 18.Genetic Testing for Heritable Mutations in the BRCA1 and BRCA2 Genes [https://www.eviq.org.au/]
- 21.Metcalfe K, Gershman S, Ghadirian P, Lynch HT, Snyder C, Tung N, Kim-Sing C, Eisen A, Foulkes WD, Rosen B, Sun P, Narod SA (2014) Contralateral mastectomy and survival after breast cancer in carriers of BRCA1 and BRCA2 mutations: retrospective analysis. BMJ 11(348):g226. doi: 10.1136/bmj.g226 CrossRefGoogle Scholar
- 22.Huzarski T, Byrski T, Gronwald J, Górski B, Domagala P, Cybulski C, Oszurek O, Szwiec M, Gugala K, Stawicka M, Morawiec Z, Mierzwa T, Janiszewska H, Kilar E, Marczyk E, Kozak-Klonowska B, Siolek M, Surdyka D, Wisniowski R, Posmyk M, Sun P, Lubinski J, Narod SA (2013) Ten-year survival in patients with BRCA1-negative and BRCA1-positive breast cancer. J Clin Oncol 31(26):3191–3196CrossRefPubMedGoogle Scholar