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Updated: Apr 17, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer
Michelle W Wong-Brown1, Cliff J Meldrum, Jane E Carpenter
1School 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.
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.
Insights
Triple-negative breast cancer (TNBC) patients have a 9.6% rate of BRCA1 or BRCA2 mutations. Genetic screening guidelines should include the triple-negative phenotype for broader testing.
Area of Science:
- Oncology
- Genetics
- Genomic Medicine
Background:
- Triple-negative breast cancer (TNBC) lacks estrogen, progesterone, and HER2 receptors, presenting unique treatment challenges.
- TNBC gene expression profiles resemble those in BRCA1 mutation carriers, suggesting a potential link.
- Existing research indicates variable BRCA mutation prevalence in TNBC patients globally.
Purpose of the Study:
- To determine the prevalence of BRCA1 and BRCA2 mutations in a cohort of triple-negative breast cancer patients.
- To compare mutation prevalence across different countries (Australia and Poland).
- To analyze the relationship between BRCA mutations and age of diagnosis in TNBC patients.
Main Methods:
- Genomic DNA from 774 triple-negative breast cancer patients (439 from Australia, 335 from Poland) was analyzed.
- Next-generation sequencing was employed to examine the entire coding regions and exon-intron boundaries of BRCA1 and BRCA2.
- Patient data, including age at diagnosis and family history, were collected and analyzed.
Main Results:
- A BRCA1 or BRCA2 mutation was identified in 74 out of 774 (9.6%) triple-negative breast cancer patients.
- Mutation prevalence was similar in Australia (9.3%) and Poland (9.9%).
- BRCA1 mutation carriers were diagnosed at a significantly younger age compared to non-carriers, while BRCA2 carriers showed no significant age difference.
Conclusions:
- The prevalence of BRCA mutations in triple-negative breast cancer warrants consideration for expanded genetic screening.
- A significant proportion of mutation-positive patients lacked a family history, highlighting the limitations of current genetic testing criteria.
- The triple-negative breast cancer phenotype should be incorporated into genetic screening guidelines to improve early detection and risk assessment.
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