Family Identity and Roles in the Context of Li-Fraumeni Syndrome: “No One’s Like Us Mutants”

Abstract

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer syndrome in which individuals have a significantly increased risk of developing multiple cancers throughout the life span. An LFS diagnosis may shift the individual’s sense of self and tolerance of cancer risk as they engage in cancer screening and cancer prevention activities. This study examined the impact of family identity on health decision making, communication, and role function. Forty-five families completed one or more interviews during an annual, protocol-specific cancer screening study. An interdisciplinary team analyzed 66 interviews using interpretive description and modified grounding theory. Thematically, identity emerged as an evolving construct regarding self and/or family, embedded in historical and ongoing experiences with LFS. Notions of individual and shared family identities guided decision making related to healthcare and influenced interpersonal communication and role function between supportive networks and families. Alignment between individual, family, and generational identities may shape engagement in genetic testing, risk management, and family life. Medical teams that are unequipped to address the psychosocial challenges that LFS populations face may include mental health professionals on interprofessional care teams to navigate risk management and consequential familial conflict.

Li-Fraumeni syndrome (LFS) is a rare hereditary cancer predisposition syndrome in which individuals experience a nearly 100 percent risk of developing multiple cancers throughout the life span (Mai et al., 2016). The most frequently occurring cancers include soft-tissue and bone sarcomas, premenopausal breast cancer, brain tumors, and adrenocortical carcinomas, among others (Kratz et al., 2017). About 70 percent of classic LFS presentations are caused by pathogenic germline variants, also called mutations, in TP53 (Schneider et al., 2019). TP53 mutations are inherited in an autosomal dominant pattern in which mutation carriers have a 50 percent chance of passing the mutation to each of their offspring (Kratz et al., 2017). Between 7 percent and 20 percent of individuals with LFS have de novo mutations, which are absent in ancestors but can be passed to offspring (Schneider et al., 2019).

Individuals with LFS experience wide variability in the timing, location, and course of cancer, with limited options for prevention. Recommended cancer screening and surveillance protocols are demanding, given the need to engage in multimodal examinations throughout the life span, e.g., physical examination, whole-body magnetic resonance imaging (MRI), brain MRI, breast MRI, mammography, colonoscopy, abdominal and pelvic ultrasounds, and blood work (Kratz et al., 2017; Villani et al., 2016). Early evidence from cancer screening trials demonstrates that cancer screening leads to early tumor detection, which has been associated with improved survival (Villani et al., 2016). Since LFS is hereditary, many of the individuals with LFS have extensive family histories of multiple, rare cancers and early death due to cancer. Individuals and families with LFS report substantial psychological burdens, not only from the rigorous screening, but also from recurrent cancer diagnoses and associated grief (Werner-Lin et al., 2020) and the emotional, physical, and financial stressors related to cancer care (Oppenheim et al., 2001). This multifaceted burden suggests that this population may experience higher cancer distress and diminished quality of life compared with individuals experiencing a sporadic (i.e., spontaneously occurring, nonhereditary) cancer diagnosis (Peterson et al., 2008).

Family Identity in Hereditary Cancer

Interpersonal relationships, such as familial relationships, play a critical role in identity development because individuals often understand their environment and ascribed roles based on the social groups to which they belong, suggesting that individual and group identities are connected (Soliz et al., 2009). Family identity can be defined using the frameworks of social identity theory (Tajfel & Turner, 1986) and self-categorization theory (Turner et al., 1987). Social identity theory suggests that an individual conceptualizes their sense of self using cognitive (sense of belonging) and emotional factors (value of belonging to that group; Tajfel & Turner, 1986). Self-categorization theory adds that this identity formation can occur at multiple levels simultaneously (i.e., individual and group), suggesting that sense of self is relational and comparative (Ashforth & Mael, 1989; Turner et al., 1987). Together, these observations suggest that family identity may be constructed at the individual and group level and may be shaped by interpersonal interactions among members who experience belongingness through shared experiences, social support, family roles, emotions, and beliefs (Acero et al., 2017; Barker et al., 2019; Leonard et al., 2017).

Family Identity in LFS

A cancer diagnosis marks a significant illness event that influences identity and self-perception based on associated physical, emotional, and financial changes (Oppenheim et al., 2001). Sporadic cancer (Richardson et al., 2017) and hereditary cancer (Klitzman, 2009) represent two distinct illness experiences that may shape family identity differently. With a sporadic cancer diagnosis, identity typically develops outside the context of a familial cancer history, and this identity may change as a diagnosis is understood. With hereditary cancers, identity develops at both individual and familial levels influenced by the treatment course, toxicities, and survival experience of prior generations as the frame of reference relative to the individual’s own cancer diagnosis (Forbes Shepherd et al., 2018). For example, women with pathogenic germline variants in BRCA1/2 often report that their risk-related management choices affected both themselves and members of their social and family networks (Ersig et al., 2019; Underhill et al., 2012; Werner-Lin et al., 2018). For couples in which one partner has an LFS diagnosis, a shared identity and various coping strategies exemplified a dyadic and family identity associated with LFS (Young et al., 2019).

Individuals with LFS are likely to have witnessed firsthand the course of multiple cancers in family members over generations, requiring ongoing adaptation to challenges associated with family caregiving, communication about genetic risk, and role change over time (Pantaleao et al., 2020; Peters et al., 2011; Werner-Lin et al., 2020). The psychosocial and biomedical features of LFS suggest that it can be usefully classified as a chronic illness (Werner-Lin & Rolland, 2006). The threat of a chronic illness brings family identity to the forefront during socialization into family beliefs and values surrounding health behaviors and decision making to manage cancer risk (Leonard et al., 2017; Leventhal et al., 2016). For example, Underhill et al. (2012) noted how women with hereditary BRCA1/2 cancer risk compared their personal narratives with their family narratives when justifying their own health behavior related choices.

Little is known about how individuals and families with LFS form identities and adapt to family and individual roles over time, and how these factors impact health decisions. Therefore, we chose to explore the concept of family identity in families with TP53-positive LFS and its impact on health decision making and role function. We hypothesized that examining family identity and the interplay between individual and family identities for those living with LFS might provide insight into intergenerational beliefs and practices, as well as individual and group coping strategies. Each of these may inform medical and psychosocial care when working with LFS individuals and other individuals and families with highly penetrant hereditary diseases.

Method

Sample and Recruitment

In 2011, the National Cancer Institute’s (NCI) longitudinal study of LFS (NCT01443468, #11-C-0255, https://www.lfs.cancer.gov) opened to accrual for individuals with LFS (TP53-positive and -unknown) and their family members (TP53-negative and -unknown). A subset of TP53-positive individuals older than three years old was invited to join the screening arm of the study with annual visits to the NCI for comprehensive examinations. The study protocol funded travel for screening cohort participants with pathogenic TP53 variants to visit the NCI annually for comprehensive physical examinations, with supportive family members invited but bearing their own travel costs. At each visit, all screening participants and their supportive family members above age 13, both mutation positive and negative, were invited to complete a family group interview (see the Appendix for a list of interview questions). Family groups varied in the number of members who were TP53 positive and negative. For example, one family group may have had three members who are TP53 positive (screening cohort participants) and one member who was TP53 negative (supportive family member). Family groups ranged in size from two to four members and comprised siblings, parent–child dyads, partners, and mixed or extended family units. Furthermore, the constellation of family members present at the NCI varied within families from year to year based on who was available to attend. Families who completed more than one interview provided updated family medical information each time. No thematic differences emerged between families who completed a single versus multiple interviews.

Design

A licensed family therapist conducted all interviews. A semistructured interview protocol was designed by the interprofessional care team including a genetic counselor, social work consultant, and the oncology medical staff. Family interviews focused on genetic testing decisions and experiences, family communication, reproductive decision making, couple relationships, and cancer prevention behaviors. Written consent was obtained from each participating individual before the start of each interview. All interviews were recorded and transcribed verbatim. Participants selected pseudonyms and all personal identifying information was removed from transcripts. Transcripts were stored on a secure, password-protected NCI–affliated computer, as were the Dedoose data analysis files. Access to research databases remains strictly limited to preapproved investigators.

Data Analysis

Interpretive description, which emerged from qualitative nursing research (Thorne, 2016), contextualizes biomedical and psychosocial experiences within preexisting empirical and practice frameworks to facilitate identifying useful practice-related findings. Researchers created a case file for each family with interview transcripts and a family pedigree. (A pedigree is a medical family tree indicating family members, names, and dates of illness diagnosis and death [NCI, n.d.].) Using the tenets of interpretive description, four researchers with qualitative training separately conducted open coding on a single interview transcript to identify in vivo codes that emerged organically during interviews (Denzin & Lincoln, 2008) and a priori codes originating from sensitizing concepts (Charmaz, 2006). After establishing a preliminary codebook, the interviewer identified three additional case files for maximum variation (definition of “qualitative research,” Patton, 2005) and the same three investigators coded them in round-robin style. All case files were then loaded into Dedoose software and double-coded by two coders who met regularly with the PI. Together, the team compiled and refined a working list of codes, then clustered them into thematic categories. In the final analysis phase, the coding team met to discuss interpretations and classify findings into recurring patterns.

Data Quality

Two researchers coding in tandem checked each other’s findings to establish consistency. A senior qualitative social work researcher provided mentorship regarding the thematic findings of the study. Prolonged exposure (Roy et al., 2015), interprofessional collaboration on coding and interpretation, and triangulation with pedigree data facilitated rigorous analysis.

Findings

Between 2012 and 2017, 45 families with 120 participants ages 13 to 81 years completed 66 interviews in varying combinations, including 26 couples, 19 parent–child dyads, 11 sibling groups, and 10 mixed or extended family groups (e.g., grandfather–grandson dyad). Of the 120 participants, 78 had confirmed pathogenic TP53 variants and 42 participants attended in a supportive capacity. Interviews ranged from 21 to 81 minutes (M = 50). The sample was consistent with previous literature in that participants were predominantly White and had a college or postgraduate degree (Peters et al., 2016).

All families but one discussed how genetic testing results, shared family beliefs about inheritance, and illness histories informed identity. For example, individuals from four different families separately and explicitly labeled themselves as “mutants.” Family groups discussed identity by describing how LFS shaped family roles, life choices, and relationships by creating unique links between affected family members. At the individual level, over half of the participants made implicit reference to identities that diverged from family narratives and beliefs by using language referencing “me” versus “them.” Two themes emerged: (1) claiming an LFS identity and (2) accepting versus rejecting LFS information and identities.

Claiming an LFS Identity

Participants with LFS described feeling uniquely connected to other family members with LFS and disconnected from those who did not have LFS. This distinction existed both within nuclear families and across extended family networks. For the individuals who had completed genetic testing, the first defining attribute set those who had tested positive and thus had LFS against those who had tested negative for their familial mutation and hence did not have LFS. Subthemes emerged revealing two processes related to developing an LFS identity: (1) family identity inclusion and exclusion criteria and (2) thresholds of severity.

Family Identity Inclusion and Exclusion Criteria

Family identities were not fixed, but rather shifted dynamically due to experiences with LFS, cancer diagnoses, loss and grief, and other syndrome-related aspects of daily life. Individuals and family groups defined their own “inclusion criteria” and “exclusion criteria” for specific identities. Criteria for an LFS identity included pursuing genetic testing, presence of a TP53 variant, TP53 variant and its penetrance, location and frequency of cancer diagnoses, experiences with cancer, and number of cancer-related deaths in the nuclear family. (Variants can also be referred to as mutations [NCI, n.d.]. Not all TP53 variants cause the same cancer patterns. Some variants have lower penetrance, i.e., the family’s cancer frequency may be lower than that observed with other variants, while still being at an elevated risk. However, it is important to note the unpredictability of cancer occurrence—families with the same TP53 variant may have very different cancer patterns of tissue of origin and age at diagnosis [Schneider et al., 2019].) LFS identities existed on a fluid spectrum in which individuals were suspended between subgroups as they accessed genetic testing and related care or decided against it.

Prior to receiving genetic testing results, some individuals and their family members speculated whether they would be mutation positive with phrases like, “I bet I’m going to get it.” The positive or negative genetic testing result irrevocably determined whether an individuals could “legitimately” identify as a person with LFS. Meeting inclusion criteria was powerful and pervasive; in some family groups, members reported distress when they tested negative:

Kerry Voga: [Kerry’s mother] was very supportive of getting testing and was almost affronted that she wasn’t the one [who] caused it [LFS].

Ethel Robin: She [Ethel’s daughter] tested negative, and I think she was a little disappointed about that [not having LFS].

These individuals had operated under the assumption that they belonged to a family subgroup only to find out that they did not have LFS. This required redefining important aspects of self with a different vision for their future, no longer concordant with what lay ahead for their affected loved ones.

A personal LFS diagnosis was not a requirement for LFS identity legitimacy. Individuals without LFS could acquire an LFS identity if their partner, or more often, their children, had LFS:

Fred Tulip: My kids, even though I don’t have the Li-Fraumeni, but since I’m living this world, the Li-Fraumeni world with them, I adapt everything to my life, and I try to learn, understand.

Fred, who does not have LFS, strongly identified with LFS despite not personally being diagnosed because he was both a parent of and partner with loved ones who had LFS. Through his lived experiences and hopes for their future together, he shared this identity.

Thresholds of Severity

Participants with LFS described their identity as having been shaped by their response to a first cancer diagnosis, or set of diagnoses, or the penetrance of the TP53 mutation. Their perception of the intensity or impact of cancer on their lives created thresholds of severity. The severity of an individual’s cancer diagnosis compared with other cancer diagnoses in their family helped particpants understand how their own cancer experiences might fit into their family narrative. For example, in the Voga family, there were three siblings with LFS and distinct personal cancer histories who reported how these experiences shaped engagement with providers, how they sought and shared LFS information, and how they understood the syndrome. Ruth remained cancer free at age 64; Kerry first experienced cancer at age 47; while Charles, now age 60, developed his only cancer at age six:

Ruth Voga: I’ve always thought I always had a chance [of having LFS], if I have two siblings with it, or three at that point. I mean, I had extra breast exams. I had regular checkups and stuff. So, it wasn’t … I mean, it was kind of a shock to me [when she tested positive for LFS], but not bad, because I’d always kind of lived with it.

Kerry Voga: Well, I mean, I probably look at it [LFS status] different because I’ve known about it for 15, 16 years, a long time. But I think … just trying to say, OK, there’s not a whole lot I can do about it. Keep myself healthy, you know, be vigilant, you know, enjoy life, and not let it consume you.

Charles Voga: For me, [having LFS] it’s just like, OK, I got blond hair, too, or whatever, you know, or I’m right-handed … I don’t put a whole lot of thought into it.

Varying experiences with LFS-related cancers influenced how each sibling came to understand LFS and its impact on their family’s narrative and individual identity. For some families, these severity comparisons were not a source of discord. However, for other families, these severity comparisions were major points of contention. Members with LFS expressed sentiments like “she doesn’t get it” when referring to perspectives shared only with other relatives whose cancer experiences were similar to theirs. According to some participants, the only way to understand an LFS-related cancer was to experience a similar level of severity, and subsequent life changes or loss, in one’s own medical care. These comparisons highlighted degrees of severity as a mechanism for who “could” and “could not” relate to or claim certain aspects of the family identity. This remained true even when all family members had mutations and cancer diagnoses. For the Mathews family, each sibling had LFS, but each experienced it differently:

Randolf Mathews: Now L [sibling], her cancers have been, not to minimize them, been more minor cancers, a thyroid and the bladder, and she is real quick to just think the future is going to be fine … so I think it’s a little hard for her to be thinking really broadly about what Vita [sibling diagnosed with breast cancer] is going through.

Severity thresholds stratified experiences with cancer treatment, survivorship, and loss within and between family groups. Participants sorted family members into subgroups based on levels of perceived severity defined by their own personal and proximal experiences with cancer and loss. Participants found shared identities and validation in these subgroups. In some families, LFS identities were disputed over perceptions regarding the classification of the specific TP53 mutation and the implications of the “mild” impact (low penetrance) for cancer expression:

Colleen Bray: Our family has been a mild case and I guess we’ve just been very fortunate that it’s been a mild case.... My aunt has had cancer twice in her lifetime, but other than that, in our immediate family, there hasn’t been any significant cancers or sickness.

For this family, only one member having cancer twice has been relatively “fortunate” compared with other LFS families who have experienced more severe presentations. Similarly, a mutation-negative woman identified her family variant as “mild,” to which her mutation-positive sister replied, “Well, it doesn’t feel very mild when you have it.” The way she perceived the severity of their family’s variant differed vastly from the perception of her sister, who did not have the mutation, because having LFS had shaped her outlook on cancer and risk, a set of challenges that she understood differently from her noncarrier sister.

Accepting versus Rejecting LFS Information and Identities

A striking distinction emerged between family groups, and between family members, who sought and accepted versus those who rejected or denied interest in pursuing LFS genetic testing and risk management information. Some families, or individuals in families, strongly believed that pursuing genetic testing was the responsible, safe action for one’s health and for all individuals at risk. Congruency between actions (i.e., receiving genetic testing) and beliefs (i.e., believing genetic testing is the “right” thing to do) were related to how these families sought out opportunities to learn about LFS risk and pursued this information in groups. This aligned with their enrollment and participation in this research study.

A subset of these participants tried communicating information about LFS with relatives who had not pursued testing or who, participants reported, vehemently denied familial risk or interest in LFS-related conversations:

Michelle Kairis: My father’s mother’s family was all closed, and said don’t contact us again [about genetic testing for LFS]. They were very upset about it and they have a history very similar to our side, like my dad’s side of the family with brain tumors, and melanomas … and all kinds of cancers.

Participants experienced this as invalidation of their own lives and their chosen management strategies aimed at maximizing their survival. Variation in how families conceptualized LFS influenced how family members experienced LFS-related cancers. The aforementioned Voga siblings further explained how members of their extended family had not been diagnosed with cancer “yet” so “it’s hard for them to get excited about it [LFS].” The extent of LFS had not yet become “real” for their extended family, enabling them to hold their LFS identity at a distance.

Discussion

Family-level analyses allowed us to define family identity, explore unique family dynamics, and examine the impact of family identity on communication of health-related information. Most participants who spoke about their LFS identity had TP53 mutations; however, there were participants who claimed an LFS identity despite being mutation negative. They were either a partner or parent to someone who had LFS, who earned their membership as critical caregivers. Participants defined parameters for how family members bonded with one another over cognitive and emotional experiences related to LFS, promoting a sense of group belonging. This finding was supported conceptually by social identity theory (Tajfel & Turner, 1986) and self-categorization theory (Turner et al., 1987) in that families in this study derived a sense of group identity through shared experiences. A previously published report on couples in this cohort demonstrated that shared identity encouraged loved ones who did not have LFS to learn about LFS and cancer risk to enable support and participation in familial health-related decision making (Young et al., 2019). Underhill et al. (2012) discussed similar group dynamics in families with BRCA1/2 mutations. Barker et al. (2019) suggested that identifying with a social group promotes adjustment to life-altering circumstances. In the context of adjusting to multiple cancer diagnoses and chronic cancer risk, family identity may serve as a buffer or protective mechanism for coping with distress.

Families who accepted information about LFS (i.e., received genetic testing, learned about LFS and cancer risk) may have been more likely to develop an LFS-related identity. This acceptance may have prompted changes to their own lifestyle and health behaviors to manage risk. These choices may impart a sense of agency when control over their health and potential future cancer is limited, similar to health behaviors observed in individuals responding to other chronic illnesses (Leventhal et al., 2016). Families who rejected information about LFS (i.e., did not pursue genetic testing, or learn about LFS and cancer risk) may have simultaneously, inadvertantly rejected an LFS-related identity by removing the possibility of learning about their potential LFS risk. In families with LFS, Peters et al. (2011) found themes suggesting that family members rejected LFS information and communication as a form of coping. However, rejection of information could pose a health threat if risk went unmonitored. The behavioral implications for these identities merits further investigation.

The heritability and highly penetrant nature of TP53-associated LFS emphasizes the need to consider family context in creating, sustaining, and evolving individual identities. The degree to which a participant claimed an LFS identity and accepted or rejected LFS-related information varied within families, and that variation created in-group/out-group dynamics. These dynamics shaped communication of genetic risk information across kindreds and led to strained relationships. LFS experiences were so prevalent for some that out-group perspectives spurred isolation and resentment. These group dynamics may relate to prior findings on communication barriers (Peters et al., 2011) and communal coping strategies (Young et al., 2019) in that the lack of a unified LFS family identity may lead to troubled communication patterns and necessitate therapeutic intervention. Competing beliefs within family groups that challenge family narratives may shape engagement with supportive networks, alter familial roles, and impede health-related information sharing across generations (Pantaleao et al., 2020).

Strengths and Limitations

These data are derived from the largest longitudinal cancer screening study for LFS and the largest extant family-based data collection. Some families completed more than one interview within the five-year data collection period, providing consistent updates for the data. Additional strong features of the study included the wide age range of participants and the active participation of family members without an LFS diagnosis. However, the sample was relatively homogenous and included only a few families with the unique Brazilian founder mutation (Achatz & Zambetti, 2016). LFS is known to affect individuals of all races and ethnicities. As our study population is mostly Caucasian, these themes might not represent all individuals and families diagnosed with LFS either in the United States or internationally. A more diverse sample may provide more nuanced findings. Some families completed single interviews, which might miss detecting potentially meaningful changes in standard care over time. Last, the sample comprised participants who were engaged in genetic research, testing, and preventive screening, suggesting the possibility of a self-report bias and limited interpretive strength regarding reports on behavior and attitudes of family members who did not participate.

Clinical Implications and Future Directions

Identities informed by cancer risk, diagnoses, and death across generations within kindreds are formed at the individual and group levels. Deeper understanding of individual and family identities may sensitize health and mental health providers to issues that shape difficult healthcare decisions, including genetic testing, cancer screening, and cancer preventive actions. Clinicians can facilitate family communication regarding identity issues in LFS, which may expand risk tolerance and address grief through meaning making (Werner-Lin et al., 2020). Long term, this type of facilitation may be particularly important as roles and identity can change over time. Moreover, clinicians may elicit views of family identity over generations to facilitate communication about genetic risk with extended family members, navigating complex family dynamics, and providing emotional support following invalidation from out-group networks. Considering LFS identity in a clinical care setting may lead to facilitating choices that appropriately reflect individuals’ understanding of illness in their family life, their beliefs about risk and treatment and values related to addressing LFS risk, and quality of life with LFS. Given the multifaceted medical and psychosocial issues this population faces, medical teams may consider utilizing a multidisiciplinary approach in providing care to individuals and families with LFS. Mental health clinicians can use this information to better assess individual and family needs while holistically and effectively supporting individuals’ right to self-determination.

A shift from focusing on individuals one at a time to individuals and families together may help build family alliances, shore up support where it is available, and challenge painful assumptions about loved ones. However, mental healthcare is often lacking in the hereditary cancer context (Werner-Lin et al., 2020; Young et al., 2019). This unmet need calls for specialized training for mental health clinicians who work in oncology spaces (Werner-Lin et al., 2016). Such training can occur either in degree-conferring programs or as continuing education workshops. This type of training should aim to familiarize clinicians and caregivers with the psychosocial challenges specific to hereditary cancer risk in families over the life course and methods for effectively supporting families with complex problem solving, group decision making, and grief.

Future research should target adolescents and young adults with LFS, or parents and their young children with LFS, to identify challenges and the process of forming an LFS identity during their formative years.

Biography

Catherine Wilsnack, MSW, LMSW, is a doctoral student, University of Texas at Austin. Jennifer L. Young, PhD, AMFT, is a postdoctoral fellow, Standford Center for Biomedical Ethics, School of Medicine, Stanford University, Stanford, CA. Shana L. Merrill, MS, LCGC, is a genetic counselor, Hospital of the University of Pennsylvania, Philadelphia. Victoria Groner, BS, MS, CGC, is a graduate of the genetic counseling program, Center for Genetic Medicine, Feinberg School of Medicine, Northwestern University, Chicago. Jennifer T. Loud, RN, DNP, CRNP, is former assistant branch chief; Renee C. Bremer, MS, is epidemiology program analyst; and Mark H. Greene, MD, is scientist emeritus; and Payal P. Khincha, MBBS, is physician scientist early investigator, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD. Allison Werner-Lin, PhD, LCSW, is associate professor, School of Social Policy and Practice, University of Pennsylvania, Philadelphia. Address correspondence to Payal P. Khincha, Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, 6E540, Besthesda, MD 20892; email: payal.khincha@nih.gov.

APPENDIX: EXCERPTED INTERVIEW GUIDE

• Please tell us about how you became aware of the TP53 mutation in your family. How did information about Li-Fraumeni syndrome (LFS) and/or genetic testing spread to other family members?

• What challenges have you faced in talking about cancer risk as a family? How has the family dealt with them?

• Is there a family belief about whether/when/which people should get tested? To what extent were each of you involved in each others’ genetic testing processes? In what ways did you participate?

• Are there family expectations about how members with LFS should manage their risk? What happens when family members disagree or make different choices about how to manage their cancer risk?

• What, if any, strategies have family members considered regarding family planning and the 50 percent chance of a child inheriting the mutation (e.g., adoption, donor gametes, preimplantation genetic diagnosis, prenatal diagnosis, etc.)?

• What information about LFS is shared with children and adolescents in the family?

• What have you learned from your own experiences with LFS and cancer, either helpful or not helpful, that you would want to pass along to younger family members? What are your hopes for the next generation with regard to LFS and cancer?