Cancer Risk Perceptions of Adolescents and Young Adults with Li-Fraumeni Syndrome: "You Do Not Know If You Have Lived Half Your Life Already"

Introduction Li-Fraumeni Syndrome (LFS) is a rare, heritable cancer predisposition syndrome characterized by near 100% chance of multiple primary malignancies, the possibility of pediatric onset, limited options for prevention, and substantial uncertainty regarding disease manifestation and prognosis. In consultations, providers communicate evidence-based cancer risk estimates to inform individuals and families with LFS about cancer susceptibility. Patient perspectives, however, may yield conceptualizations of risk that accumulate beyond the diagnostic, to encompass threats to health and wellbeing across developmental, emotional, and familial domains. These nuanced and multifaceted perspectives may shape distress, coping, and life-long adaptation to cancer risk. This study used a patient-centered approach to examine the nature of risk perceptions of adolescents and young adults’ (AYAs) with LFS.

Methods: A senior social work researcher led an interprofessional team of health communication, occupational science, social psychology, and genetic counseling experts. The team recruited thirty-eight AYAs (16-38 years) enrolled in a national, federally funded study of families with LFS. Each participant completed an in-depth, semi-structured interview with a study investigator. The interview guide focused on individual and family cancer histories, experiences with health providers, activities of daily living, family and social networks, and existential perspectives regarding LFS. Interviews were recorded, transcribed verbatim, and coded using techniques of interpretive description and modified grounded theory. The team developed a codebook through consensus. Rigor was ensured through multiple readings of each transcript, regular debriefing, triangulation with family pedigrees, and collaboration with medical experts.

Findings: Participants described dynamic meaning-making regarding cancer risk, nested in family experiences of cancer, reduced physical functioning, anticipatory loss, and cancer-related death. Few participants articulated numerical risk figures. The familial nature of LFS meant participants were often coping with multiple, overlapping, and dynamic uncertainties about their own and their loved ones’ quality of life and survival. Some perceived uninformed health providers increased their risks via conservative management of scans or by dismissing worrisome symptoms. Beyond diagnostic risks, participants described psychosocial risks, including: poor mental health (e.g., anxiety, intrusive thoughts), assuming family roles after an LFS-related death (e.g., parenting), and family dynamics challenged by chronic caregiving and grief. Beliefs about risks to health and mental health also shaped perceptions of achievable life goals common to the adolescent and young adult years, constituting an additional domain of risk and loss. These included investment in academic/professional achievement, selection of life partners, and reproductive decision making, which constituted an additional domain of risk. Participants described protective health behaviors (e.g., diet, exercise, hobbies) as attempts to mitigate risks to health and mental health by increasing perceived control, improving quality of life, and protecting loved ones from the distress of another cancer diagnosis.

Conclusions: Perceptions of familial cancer risk are nested in complex family histories that evolve over time alongside distress and coping, suggesting the need for longitudinal research using developmental and family frameworks. Given the fluidity and nuanced nature of risk perception, social work-led interprofessional teams are uniquely positioned to design holistic interventions and conduct high-impact translational research on patient-centered care with AYAs with LFS.