Abstract 5598: Germline TP53 mutation in very early onset breast cancer patients without BRCA1 and BRCA2 mutation in Brazilian population

Germline mutations in TP53 gene are the main cause of cancer susceptibility in the Li-Fraumeni syndrome (LFS) and its variant, Li-Fraumeni-like syndrome (LFL). It is associated with the development of early-onset cancers, including early onset breast cancer, sarcomas, brain tumors and adrenocortical carcinoma. Breast cancer is the most common tumor found in the LFS/LFL accounting for more than 27% of all tumors described. Recently, the 2010 National Comprehensive Cancer Network guidelines for Hereditary Cancer indicated that TP53 germline mutation testing should be considered for women with breast cancer before age 30 years without a BRCA1/BRCA2 mutation detected. The aim of this study is to identify the role of germline mutations in TP53 gene in women with early onset breast cancer who do not carry a BRCA1 or BRCA2 mutation, regardless of family history. Germline DNA was obtained from peripheral blood, collected after genetic counseling and signature of informed consent. TP53 mutation status was assessed by DNA sequencing of the entire coding region of TP53 gene (exons 2-11). A total of 41 females who developed ductal invasive breast cancer were selected, including (a) 15 women diagnosed with very early breast cancer (VEBC), before age 30, regardless of family history of cancer and (b) 26 women diagnosed with early breast cancer (EBC), between ages 30 and 36 years old, regardless of family history of cancer. One patient from the VEBC was found to be carrier of a germline missense mutation detected occurred in the DNA binding domain of the TP53 gene, p.V143M, (GTG