DETECTION RATE OF GERMLINE TP53 P.R337H AMONG WOMEN AT RISK OF HEREDITARY BREAST CANCER IN A PUBLIC HEALTH SYSTEM OF MIDWEST BRAZIL

Keywords:

hereditary breast cancer syndrome - public health - Li Fraumeni Syndrome

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. Objective: To evaluate the detection rate of TP53 p.R337H in patients (pts) at risk of hereditary breast cancer (HBC). Methodology: Hereditary cancer risk assessment based on the National Comprehensive Cancer Network Criteria (NCCN)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 NCCN criteria were referred for genetic counseling and genetic testing. For those patients who could not afford a genetic panel, a PCR test specifically for TP53 p.R337H variant was performed. In case of p.R337H detection in the proband, genetic counseling and PV 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 multigene panel testing. This cohort was mostly represented by pts from the Brazilian Midwest (47%) and Northeast (35%). The median age of BC diagnosis was 44 y.o. (18 - 78). Invasive ductal carcinoma represented 92% of the tumors, 50% were ER/PR+ HER2-, 25% HER2 +, 25% 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). The family members from these two families received genetic counseling and genetic testing. Cascade testing was able to identify 12 additional carriers. All carriers are in 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 DFPublicHealth 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. Despite the low detection rate ofp.R337H (in comparison to other Brazilian studies from the South), there was a high familial impact through cascade testing.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
03 November 2022