Abstract 1814P
Background
Germline pathogenic variants in the TP53 gene are the underlying cause of Li-Fraumeni Syndrome (LFS). Carriers are at risk for a wide tumor spectrum. Lung cancer (LC) represents 3.6% of all LFS tumors and most LC in LFS harbor EGFR mutations. LFS is present in 0.3% in South and Southeastern Brazil due to the founder p.R337H TP53 variant. We aim to evaluate the prevalence and outcomes of p.R337H TP53 carriers with LC.
Methods
We conducted a single-center retrospective descriptive analysis of patients (pts) from the Brazilian Li-Fraumeni Syndrome Study (Brazilian LI-Fraumeni Syndrome Study - BLISS). 275 TP53 p.R337H pts were analyzed and 135 had a personal history of cancer. All consecutive pts who received a diagnosis of LC were included in this study.
Results
We found 18/135 pts (13.3%) with p.R337H in the BLISS database. Median age at LC diagnosis was 55 y.o. (33-72), 12 (66.7%) female and 10 were non-smokers. All LC pts presented lung adenocarcinoma (LA). Eight pts (44.4%) developed more than one primary cancer during their follow-up. In nine pts (50%), LC was the index diagnosis of LFS. Most LC pts were diagnosed with either early stages or locally advanced disease (14/18 pts, 77.8%), and the remaining four pts presented with de novo metastatic disease. Molecular evaluation (NGS or PCR- based tests) was performed in 11 cases. EGFR-activating mutations (EGFRmut) were detected in six pts: three L858R, one exon 19 deletion, one exon 20 insertion, and one with two mutations (L858R and exon 20 insertion). In these six pts with EGFRmut tumors, the median age at LC diagnosis was 52 y.o. (35-59), five were female, all were non-smokers, presenting with locally advanced (three pts) or metastatic (three pts) disease. Five pts received an EGFR-TKI as first-line treatment: partial response was observed in 4/4 evaluable pts (100%), and median progression-free survival was not reached.
Conclusions
Most p.R337H TP53 carriers with LC here studied were diagnosed with tumors harboring somatic EGFR activating mutations. Our study suggests an association between p.R337H TP53 and somatic mutations in EGFR may facilitate lung tumorigenesis. EGFR-mutated Brazilian LC pts, especially young non-smokers, should be considered for genetic counseling and germline testing for p.R337H TP53.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. de Castro Jr.: Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Yuhan. All other authors have declared no conflicts of interest.