Abstract 2749: Cumulative cancer risk in the NCI Li-Fraumeni Syndrome Cohort
Authors: Mai Phuong L. , Rosenberg Philip S. , Peter June A. , DeCastro Rosamma , Khincha Payal P. , Loud Jennifer T. , Bremer Renee , Savage Sharon A. 
Published: August 2015

Abstract
Background:
Li-Fraumeni Syndrome (LFS) is a rare hereditary cancer predisposition syndrome characterized by the early onset of a wide range of cancers and a very high lifetime cumulative cancer risk. Despite significant progress in understanding LFS, uncertainty remains regarding the cancer incidence rates and cancer spectrum for TP53 mutation carriers. In addition, the cancer incidence for members of families meeting the clinical diagnostic criteria of LFS or Li-Fraumeni like (LFL) syndrome but in which no TP53 mutation has been identified (TP53- families) has not been established.
Methods: The NCI's LFS Study (NCT01443468) is a natural history study that opened to accrual in August 2011. Inclusion criteria include LFS or LFL syndrome; a germline TP53 mutation; or a personal history of choroid plexus carcinoma, adrenocortical carcinoma (ACC), or ≥3 primary cancers. Participants complete a detailed family history and individual information questionnaires. Confirmation of all reported cancer diagnoses is pursued.
Results: Of the 122 families enrolled to date, 95 families have a germline TP53 mutation (TP53+ families) and 27 are TP53-families.
TP53+ families: 243 mutation carriers from 95 mutation-positive families were included in the cancer risk estimates. The cumulative risk to first cancer diagnosis for the entire group is 43% by age 30 and close to 100 by age 70, with males having higher risk in childhood adolescence and females having higher risk starting in the 20s, mostly due to breast cancer. When examined by cancer type, the cumulative risk to age 70 is 35% for breast cancer, 16% for soft tissue sarcoma, 10% for brain cancer, 7% for bone cancer, 2% for leukemia, 2% for ACC, and 26% for others. Overall survival is approximately 80% by age 50.
TP53- families: The underlying etiology contributing to cancer risk in the TP53- families is not known at this time; therefore, for the estimation of cancer risk among these families, we included all bloodline members belonging to the lineage contributing to the eligibility criteria. Among the 522 individuals from the 27 TP53- families, the cumulative risk to first cancer diagnosis is 7% by age 30 and 45% by age 70. The lifetime cumulative risk is higher for breast, brain, lung cancer, and melanoma compared with other cancer types. Overall survival is approximately 90% by age 50.
Conclusion: We report the cumulative cancer incidence and overall survival among TP53 mutation carriers in TP53+ families as well as among members of TP53- families. Identification of additional causative gene(s) in TP53- families will help refine the cancer risk of family members. We are evaluating the risks of second primary cancers, and whether the rate is dependent on the type of the first cancer in all families.
Citation Format: Phuong L. Mai, Philip S. Rosenberg, June A. Peter, Rosamma DeCastro, Payal P. Khincha, Jennifer T. Loud, Renee Bremer, Sharon A. Savage. Cumulative cancer risk in the NCI Li-Fraumeni Syndrome Cohort. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2749. doi:10.1158/1538-7445.AM2015-2749