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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

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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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Corresponding author

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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