Breaking through Barriers: Identifying Healthcare Challenges for Adolescents and Young Adults Living with Li-Fraumeni Syndrome

Background and Purpose: Li-Fraumeni syndrome (LFS) is a rare hereditary cancer predisposition syndrome in which individuals with a germline pathogenic TP53 variant experience nearly 100% lifetime risk of developing multiple cancers starting from birth. LFS-related cancers vary in the timing, location, and presentation, with limited options for prevention. Recommended cancer screening protocols use high-interval multimodal examinations, which can be physically and emotionally demanding. Individuals with LFS report significant psychological burden related to fear of cancer diagnoses, chronic grief, and strain on emotional, physical, and financial resources. Needs may vary across lifespan phases, notably for adolescents and young adults (AYA; defined as aged 15-39 years by the World Health Organization) facing a demographically dense period of life cycle development. This study examined how AYAs with LFS navigated healthcare challenges and identified pathways to overcome them.

Methods: Researchers interviewed 38 AYAs enrolled in the National Cancer Institute’s LFS Study. Participants, who were predominantly female (n=26) and white (n=31), completed an in-depth, semi-structured interview via telephone or in-person. Interviews were recorded, transcribed verbatim, and uploaded to Dedoose™, a qualitative data management software program. An interdisciplinary team used interpretive description and modified grounding theory to analyze data. All transcripts were coded independently by two researchers. Emergent findings were discussed during weekly team meetings.

Findings: The majority of participants enrolled in the LFS Study’s cancer screening arm (versus the control arm) reported that the NCI study was their main resource for cancer screening care annually. For some, access to this care prompted study enrollment. NCI-based cancer screening care provided participants with a way to remain vigilant about early detection and clear screening results allowed for short-term relief from anxiety associated with anticipated diagnoses. Participants reported that inadequate financial resources and poor insurance coverage created barriers to pursuing cancer screening at the recommended intervals outside of the NCI study, paying for cancer treatment, and managing the demands of survivorship. Participants also faced emotional hardships associated with life cycle milestones during cancer diagnoses and treatment, or undergoing regular screening. These included completing educational programs, career development, disclosing and discussing the varied impacts of LFS with romantic partners, considering a child inheriting the familial variant, caring for sick relatives, and addressing end of life decisions. Participants described dissatisfying, invalidating interactions with healthcare providers who were unfamiliar with LFS or with reproductive options to prevent the birth of a child with LFS (e.g., preimplantation genetic diagnosis). To address these barriers, participants engaged in self-advocacy through role reversal with physicians where they acted as health educators and presented evidence for appropriate and responsive LFS care.

Conclusion and Implications: AYA’s with LFS experience multiple unmet healthcare needs and challenges that are exacerbated by a lack of age-appropriate resources. Analysis of self-advocacy practices enables a strengths-based perspective which may inform design of future supportive interventions. Developing resources for both patients and providers to address these hardships are critical to optimizing health, mental health, and financial care for AYAs and their families.

Acknowledgements: NIH Protocol 11-C-0255, ClinicalTrails.gov; NCT01443468; www.lfs.cancer.gov