Abstract PO5-08-09: Li Fraumeni Syndrome in Breast Cancer Patients of Ceará/Brazil: correlations of genotype - fenotype
Authors: Ana Rosane Sant' , Fernandes Isabelle Joyce , Luciano Maria Claudia , Bezerra Maria Julia , Bitencourt Flavio , Albuquerquye Clarissa , Silva Paulo Goberlanio , De Moura José Fernando , Oliveira Francisca Fernanda 
Published: May 2024

Abstract
Introduction: Li Fraumeni Syndrome (LFS) is a rare condition determined by germline mutation of TP53 gene. LFS has penetrance near 100% with a broad spectrum of malignances such as breast, lung, sarcomas, choroid plexus, adrenocortical carcinomas, gliomas, leukemia and other starting from early childhood. Breast cancer is the most frequent cancer type of adults with LFS, followed by soft tissue sarcomas. Individuals with LFS has an aggressive prognosis of multiple neoplasms lifetime. In Brazil the most described variant of TP53 is c.1010G &gt;A; p.R337H (the Brazilian variant). This variant affects predominantly individuals of South and Southeastern regions. Usually presents with the same spectrum of tumor of other variants however R337H presents lower penetrance, higher frequency of adrenocortical carcinomas, later onset of tumors. Ceará is a northeastern state of Brazil highly miscegenated distinct from populations of South where predominates European colonization. At Ceará originals there are no description of R337H. The present study describes Clinical and tumoral caractheristics of breast cancer patients with LFS of Cancer Reference Center of Ceará. Methods: from 2018 to 2021 breast cancer patients admitted in Instituto do Câncer do Ceará-ICC filling NCCN criteria for hereditary breast cancer were screened for germline variants. After assigned consent it was offer NGS germline genetic panel of 33 genes and clinical and pathologic data were recorded. Results: 460 BC patients were recruited, of them 6 had germline pathogenic mutation of TP53. Table 1 list these women and their variants. The mean age of the first tumor was 30 years (range 18-44), only one patient had no knowledge of familiar history (HF) of child and adults cancer, all the other listed HF of early onset of breast cancer, lung cancer, osteosarcoma, rabdomyosarcoma, GBM and gastrointestinal cancers. One had bilateral metachronic breast cancer, 3 of them had HER2 positive tumor, 1 had a metaplasic TNBC, and 1 had a Luminal B tumor. 2 variants were not found at populational database (a exons 2-10 microdeletion and a c.637C &gt;T variant). About half of relatives recruited for genetic test confirmed to the carriers and 3 of them developed neoplasms (GBM and breast cancer). Two patient had early recurrence (one of them had a third tumor of ovarian – carcinosarcoma) and died at age of 30 and 39 years old. Conclusion: The Northeast of Brazil has a distint clinical and genetic pattern of LFS from the South. No R337H variant were found in our population. We identified different variants in all patients with LFS. The BC subtype more commom was HER2 positive. The bias of our study is the original objective that evolved determination of prevalence of hereditary breast and ovarian cancer. Based on these results we are now recruiting exclusively cancer patients with clinical criteria for LFS.
Table 1 - LFS patients caractheristics
Citation Format: Rosane Sant' Ana, Isabelle Joyce Fernandes, Maria Claudia Luciano, Maria Julia Bezerra, Flavio Bitencourt, Clarissa Albuquerquye, Paulo Goberlanio Silva, José Fernando De Moura, Francisca Fernanda Oliveira. Li Fraumeni Syndrome in Breast Cancer Patients of Ceará/Brazil: correlations of genotype - fenotype [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-08-09.