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Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer

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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.

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Abbreviations

BRCA:

Breast cancer susceptibility gene

DNA:

Deoxyribonucleic acid

PARP:

Poly (adenosine diphosphate)-ribose polymerase

TNBC:

Triple-negative breast cancer

UV:

Unclassified variant

pCR:

Pathological complete response

References

  1. Dite GS, Jenkins MA, Southey MC, Hocking JS, Giles GG, McCredie MR, Venter DJ, Hopper JL (2003) Familial risks, early-onset breast cancer, and BRCA1 and BRCA2 germline mutations. J Natl Cancer Inst 95(6):448–457

    Article  CAS  PubMed  Google Scholar 

  2. Nathanson KL, Wooster R, Weber BL (2001) Breast cancer genetics: what we know and what we need. Nat Med 7(5):552–556

    Article  CAS  PubMed  Google Scholar 

  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):1082–1089

    Article  PubMed Central  CAS  PubMed  Google 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):2310–2318

    Article  CAS  PubMed  Google Scholar 

  5. Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 4(10):814–819

    Article  CAS  PubMed  Google Scholar 

  6. Anglian Breast Cancer Study Group (2000) Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. BJC 83(10):1301–1308

    Article  PubMed Central  Google Scholar 

  7. Peto J, Collins N, Barfoot R, Seal S, Warren W, Rahman N, Easton DF, Evans C, Deacon J, Stratton MR (1999) Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. JNCI 91(11):943–949

    Article  CAS  PubMed  Google Scholar 

  8. Hartman AR, Kaldate RR, Sailer LM, Painter L, Grier CE, Endsley RR, Griffin M, Hamilton SA, Frye CA, Silberman MA et al (2012) Prevalence of BRCA mutations in an unselected population of triple-negative breast cancer. Cancer 118(11):2787–2795

    Article  CAS  PubMed  Google 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):353–362

    Article  CAS  PubMed  Google 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):1234–1238

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Young SR, Pilarski RT, Donenberg T, Shapiro C, Hammond LS, Miller J, Brooks KA, Cohen S, Tenenholz B, Desai D et al (2009) The prevalence of BRCA1 mutations among young women with triple-negative breast cancer. BMC Cancer 9:86

    Article  PubMed Central  CAS  PubMed  Google 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):R142

    Article  PubMed Central  PubMed  Google 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–E1240

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  15. Evans DG, Howell A, Ward D, Lalloo F, Jones JL, Eccles DM (2011) Prevalence of BRCA1 and BRCA2 mutations in triple negative breast cancer. J Med Genet 48(8):520–522

    Article  CAS  PubMed  Google 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):145–153

    Article  PubMed Central  CAS  PubMed  Google 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/]

  19. Rennert G, Bisland-Naggan S, Barnett-Griness O, Bar-Joseph N, Zhang S, Rennert HS, Narod SA (2007) Clinical outcomes of breast cancer in carriers of BRCA1 and BRCA2 mutations. N Engl J Med 357(2):115–123

    Article  CAS  PubMed  Google Scholar 

  20. Byrski T, Gronwald J, Huzarski T, Grzybowska E, Budryk M, Stawicka M, Mierzwa T, Szwiec M, Wisniowski R, Siolek M et al (2010) Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 28(3):375–379

    Article  CAS  PubMed  Google Scholar 

  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

    Article  Google 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):3191–3196

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

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.

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Authors and Affiliations

  1. 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

    Michelle W. Wong-Brown & Rodney J. Scott

  2. Division of Molecular Medicine, Pathology North, NSW Pathology, Lookout Road, Newcastle, 2305, NSW, Australia

    Cliff J. Meldrum & Rodney J. Scott

  3. Australian Breast Cancer Tissue Bank, University of Sydney at the Westmead Millennium Institute, Westmead, NSW, Australia

    Jane E. Carpenter & Christine L. Clarke

  4. Familial Breast Cancer Research Unit, Women’s College Research Institute, Toronto, Canada

    Steven A. Narod

  5. Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland

    Anna Jakubowska, Helena Rudnicka & Jan Lubinski

Authors
  1. Michelle W. Wong-Brown
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  2. Cliff J. Meldrum
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  3. Jane E. Carpenter
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  4. Christine L. Clarke
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  5. Steven A. Narod
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  6. Anna Jakubowska
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  7. Helena Rudnicka
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  8. Jan Lubinski
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  9. Rodney J. Scott
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Correspondence to Rodney J. Scott.

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Wong-Brown, M.W., Meldrum, C.J., Carpenter, J.E. et al. Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer. Breast Cancer Res Treat 150, 71–80 (2015). https://doi.org/10.1007/s10549-015-3293-7

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  • DOI: https://doi.org/10.1007/s10549-015-3293-7

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