Abstract PS5-10-04: Willingness to participate in a trial comparing standard genetic counseling versus genetic counseling with personalized cancer risk estimates in patients with Li-Fraumeni syndrome

Abstract Background: Li-Fraumeni Syndrome (LFS), due to germline pathogenic/likely pathogenic variants (PV/LPV) in TP53, is an inherited cancer syndrome with elevated risks for early-onset breast cancer, sarcomas, brain tumors, leukemia, or a combination of multiple cancers. Unlike other hereditary cancer syndromes with personalized risk assessment tools like BRCAPRO™ or MMRPRO™ (Berry, Iversen et al. 2002, Chen, Wang et al. 2006) that are tailored by variables specific to the individual, no validated models currently exist for Li-Fraumeni Syndrome (LFS). As a result, standard genetic counseling (GC) for individuals at risk for, or diagnosed with, LFS currently include only generalized lifetime risk predictions for cancer risk. This study aims to understand patients’ willingness to participate in a randomized trial comparing standard GC practice to personalized GC via a risk model in development known as LFSPRO (Peng, Bojadzieva et al. 2017, Nguyen, Dodd-Eaton, Corredor et al. 2024, Nguyen, Dodd-Eaton, Peng et al. 2024). LFSPRO intends to estimate the likelihood of a proband to test positive for LFS and provide cancer-specific risks of a first and second primary cancer based on personal and family history details. Methods: English-speaking individuals 15 years of age or older, or the parent/guardian of those under age 15, that underwent GC for TP53 genetic testing, and those that tested positive for a PV/LPV in TP53, were eligible to participate. Those eligible were invited by secure email via their medical record to complete the questionnaire. A hypothetical clinical trial scenario in which patients are randomized to receive one of two types of post-disclosure GC approaches was provided. Approach one was standard GC defined as generic risk predictions associated with TP53 PV/LPV and routine surveillance/management recommendations. Approach two was GC informed by LFSPRO data that requires personal and family history details to predict their specific cancer risks. The questionnaire obtained additional demographic and clinical characteristic details and perceived benefits and barriers to research participation. Results: Our initial analysis shows that the return questionnaire rate for invited participants was 17.9% (65/364). Most of the participants strongly agreed or agreed to participate in the hypothetical trial (81.5%, 53/65), additionally, 76.9% (50/65) would prefer to receive personalized GC. While only 7.7% (5/65) reported having previously participated in a clinical trial, most were interested in participating in research studies (76.9%, 50/65), and even further, 66.2% (43/65) strongly disagreed or disagreed with feeling uncomfortable being randomly assigned as participants to different study groups. A review of open responses to why individuals may want to participate identified four common themes: 43.5% (20/46) had a desire to help others with LFS, 39.1% (18/46) wanted additional information to help their own health management, 34.8% (16/46) wanted to improve research and knowledge about LFS, and 32.6% (15/46) wanted to help their own family. Conclusion: Despite the low response rate, individuals in this study report interest and willingness to participate in a hypothetical randomized trial comparing standard GC and personalized GC for LFS to further the research and understanding of how to use this information in a practical way. Funding: This research is supported by the Cancer Research and Prevention Institute of Texas (RP200383). Citation Format: A. H. Woodson, J. L. Corredor, J. Voller, J. Casey, S. Green, S. Shanker, S. K. Peterson, W. Wang, B. K. Arun. Willingness to participate in a trial comparing standard genetic counseling versus genetic counseling with personalized cancer risk estimates in patients with Li-Fraumeni syndrome abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-10-04