Breast Cancer Research and Treatment

, Volume 150, Issue 1, pp 71–80 | Cite as

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

  • Michelle W. Wong-Brown
  • Cliff J. Meldrum
  • Jane E. Carpenter
  • Christine L. Clarke
  • Steven A. Narod
  • Anna Jakubowska
  • Helena Rudnicka
  • Jan Lubinski
  • Rodney J. ScottEmail author
Preclinical Study


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.


Triple-negative breast cancer BRCA1 BRCA2 Germline mutations Prevalence Genetic testing 

List of abbreviations


Breast cancer susceptibility gene


Deoxyribonucleic acid


Poly (adenosine diphosphate)-ribose polymerase


Triple-negative breast cancer


Unclassified variant


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.

Supplementary material

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Supplementary material 1 (DOCX 16 kb)
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Supplementary material 2 (DOCX 41 kb)
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Supplementary material 3 (DOCX 22 kb)


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Michelle W. Wong-Brown
    • 1
  • Cliff J. Meldrum
    • 2
  • Jane E. Carpenter
    • 3
  • Christine L. Clarke
    • 3
  • Steven A. Narod
    • 4
  • Anna Jakubowska
    • 5
  • Helena Rudnicka
    • 5
  • Jan Lubinski
    • 5
  • Rodney J. Scott
    • 1
    • 2
    Email author
  1. 1.School of Biomedical Sciences & Pharmacy, Centre for Information-Based Medicine, Hunter Medical Research InstituteUniversity of NewcastleNewcastleAustralia
  2. 2.Division of Molecular MedicinePathology North, NSW PathologyNewcastleAustralia
  3. 3.Australian Breast Cancer Tissue BankUniversity of Sydney at the Westmead Millennium InstituteWestmeadAustralia
  4. 4.Familial Breast Cancer Research UnitWomen’s College Research InstituteTorontoCanada
  5. 5.Department of Genetics and PathologyPomeranian Medical UniversitySzczecinPoland

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