RESUMO
BACKGROUND: Triple negative breast cancer (TNBC) has been classified as a disease subgroup defined by the lack of expression of estrogen and progesterone receptors as well as the absence of the human epidermal growth factor receptor-2 (HER2) overexpression. Germline mutations in the BRCA1 gene have been associated with TNBC. Approximately 70% of breast cancers arising in BRCA1 mutation carriers and up to 23% of breast cancers in BRCA2 carriers display a triple negative phenotype. However, the contribution and the frequency of BRCA1 mutations in individuals with TNBC, not specifically selected for age at diagnosis or enriched family history of breast/ovarian cancer, have not been investigated in the Tunisian population and are to be established. The aim of the present study was to assess the contribution and the prevalence of recurrent BRCA1 germline mutation (5382inC) in Tunisian women with TNBC unselected for family history or age at onset. METHODS: For BRCA1 5382inC mutation detection, the exon 20 coding region and exon-intron boundaries of BRCA1 was analyzed using direct DNA sequencing. A total of 33 DNA samples from Tunisian women diagnosed with TNBC and unselected for family history or age at onset were analyzed. RESULTS: The 5382inC mutation was identified in 2 out of 33 women with TNBC with an overall prevalence of 6% (2/33). The detection rate of the 5382inC mutation among TNBC women with family history of breast cancer was 25% (2/8). The two 5382inC mutation carriers were postmenopausal and diagnosed at the age of 50 and 57. When stratified by age, the frequency of BRCA1 mutation in patients diagnosed at age ≥ 50 years was 8.7% (2/23). CONCLUSIONS: Our results confirm a noticeable contribution of BRCA1 5382inC mutation in TNBC development in Tunisia and further indicate that screening for 5382insC mutation in the BRCA1 gene is of interest in genetic testing in our population. Additionally, our data highlight that receptor triple negativity could be an effective selection criterion for BRCA1 genetic test in our population and should therefore be considered in genetic testing guidelines in Tunisia.