Abstract OT2-12-01: Clinical Application of LFSPRO: A Prospective Study

Abstract Background: Individuals with Li-Fraumeni Syndrome (LFS) have increased risk of developing cancers of several types, such as early-onset breast cancer, soft-tissue/bone sarcoma, leukemia, brain tumors, and more, throughout their lifetime. LFS is primarily caused by autosomal dominant germline mutations in the TP53 tumor suppressor gene. It is difficult to identify TP53 mutation carriers because of the overlap in the occurrence of multiple cancer types in LFS with other inherited cancer syndromes. In order to improve the accuracy of risk assessment for these families, the LFSPRO risk model was created to predict the likelihood of a proband having LFS based off detailed patient and family history information, as well as predict cancer-specific risks for patients who have already been identified as having LFS. Specific Aims: The primary aim of this study is to evaluate the concordance of LFSPRO and clinical criteria in predicting TP53 mutation status in patients undergoing germline TP53 testing. Trial Design: After receiving standard genetic counseling, patients identified as concerning for a potential TP53 mutation by a MD Anderson genetic counselor (GC) are run through LFSPRO. LFSPRO TP53 mutation carrier risk, whether the patient meets Chompret and/or Classic criteria, decision to test, and genetic test results are collected. Select GCs are then asked to complete a survey regarding their experience with LFSPRO. Eligibility Criteria: Through standard genetic counseling practice, MD Anderson GCs identify patients with a clinical suspicion for a TP53 germline mutation. All patients identified are run through LFSPRO. Out of these identified patients, select GCs that participated in the initial genetic counseling session are asked to complete a survey over their experience using the LFSPRO. Statistical methods: We will evaluate the concordance in the prediction of TP53 mutation carrier status between LFSPRO and current clinical criteria as compared to the outcome of genetic testing results. We will cross-tabulate the predicted TP53-mutation status (positive vs. negative) with the carrier status in a 2 × 2 table and calculate the sensitivity and specificity of each prediction tool separately (LFSPRO, clinical criteria), with 95% confidence interval. Accrual: Currently, 72 patients have been run through LFSPRO. Select GCs have completed the survey regarding their experience with LFSPRO on 20 of these patients. Data collection began in December 2021 and is currently ongoing. Funding: This research is supported by the Cancer Research and Prevention Institute of Texas. Contact: Jacynda Woodman-Ross, MS, CGC, The University of Texas MD Anderson Cancer Center, jawoodman@mdanderson.org Citation Format: Jacynda Woodman-Ross, Elissa Dodd-Eaton, Jessica Corredor, Sierra O. Green, Nam H. Nguyen, Nathaniel Hernandez, Courtney D. DiNardo, Wenyi Wang, Banu K. Arun. Clinical Application of LFSPRO: A Prospective Study [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 OT2-12-01.