Abstract P5-03-19: Frequency of germline TP53 p.R337H variant among women at risk of hereditary breast cancer in a public health system of Central-West of Brazil
Authors: Correa Tatiana S. , Sandoval Renata L. , Oliveira Eduarda S. , Leite Ana Carolina R. , Weis Luiza Nardin , Achatz Maria Isabel , Oliveira Claudiner P. , Asprino Paula Fontes , Barroso-Sousa Romualdo 
Published: March 2023

Abstract
Background: Breast Cancer (BC) is one of the most common cancers diagnosed in Li-Fraumeni Syndrome (LFS). Most studies about the frequency of germline pathogenic variant (PV) TP53 p.R337H have been conducted in the South and Southeastern regions of Brazil reaching rates as high as 8% of detection. There is a lack of data on the frequency of this germline PV in other Brazilian regions, especially among patients without access to genetic tests. Objective: This study aims to evaluate the detection rate of TP53 p.R337H in patients (pts) at risk of hereditary breast cancer (HBC) and describe the clinical and demographic profile of the study cohort. Methodology: Hereditary cancer risk assessment based on the National Comprehensive Cancer Network Criteria (NCCN), version 1.2020, was performed in women with BC who were being followed in a public hospital (DF, Brazil) between January 2021 and January 2022. All pts eligible for germline genetic testing according to HBC NCCN criteria were referred for genetic counseling and genetic testing. For those patients who could not afford a comprehensive genetic test, a real time PCR test specifically searching for TP53 p.R337H variant was performed. In case of TP53 p.R337H detection in the proband, genetic counseling and familial variant testing were offered to family members. Results: Among 221 pts eligible for this study, 180 pts performed germline testing, including 100 pts tested only for the TP53 p.R337H variant (real-time PCR) and 80 pts performed out of pocket BC multigene panel testing (including TP53 sequencing). This cohort was mostly represented by pts from Central-West (47%) and Northeast (35%) regions of Brazil. The median age of BC diagnosis was 44 y.o. (18 - 78). Invasive ductal carcinoma represented 92% (n=203) of the tumors, 50% were ER/PR+ HER2-, 25% HER2 +, 25% ER/PR- HER2- (triple negative). Regarding stage at diagnosis, 59% (n=130) were stages IIB-IIIC and 13% IV. The detection rate of TP53 p.R337H was 1.1% (2/180). Among the pts who met the revised Chompret criteria for LFS, this frequency was 5% (2/40). One of them was diagnosed with a stage IIIB IDC ER/PR+HER2- at 28 y.o. and had no relevant family history of cancer. The other pt was diagnosed with a stage IV IDC ER/PR+HER2- at 44 y.o. and the family history revealed four sisters and one niece with BC, and one nephew with brain tumor at 4 y.o. The family members from these two families received genetic counseling and genetic testing. Cascade testing was able to identify 12 additional carriers. All carriers were referred for post-testing follow-up. Conclusion: According to these results, we expect to identify at least one p.R337H carrier in each 90 BC pts treated in the Federal’s District Public Health setting who fulfill HBC NCCN criteria. In a limited resources setting, in Brazil, testing the TP53 p.R337H variant with PCR is a low-cost test that should be considered at least for pts that meet the revised Chompret criteria. The overall detection rate of TP53 p.R337H carriers was lower in comparison to other Brazilian studies from the South/Southeast of the country. Both cases identified in this cohort had advanced local disease or metastatic disease at BC diagnosis, raising the concern about the importance of LFS diagnosis, and high-risk surveillance and risk reduction strategies in this subgroup of pts. Despite the low detection rate of TP53 p.R337H in this cohort, there was a high familial impact through cascade testing.
Citation Format: Tatiana S. Correa, Renata L. Sandoval, Eduarda S. Oliveira, Ana Carolina R. Leite, Luiza Nardin Weis, Maria Isabel Achatz, Claudiner P. Oliveira, Paula Fontes Asprino, Romualdo Barroso-Sousa. Frequency of germline TP53 p.R337H variant among women at risk of hereditary breast cancer in a public health system of Central-West of Brazil [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-19.