Genetic testing for hereditary cancer syndromes: patient recommendations for improved risk communication

Abstract Background Multi‐gene panel testing is replacing single‐gene testing for patients with suspected hereditary cancer syndromes. The detection of a hereditary cancer syndrome allows tested individuals to initiate enhanced primary and secondary prevention efforts—where available—with a view to reduce disease burden. Current policy prevents testing programmes from communicating genetic test results with potentially affected family members, yet it is well documented that tested individuals face multiple challenges in initiating such discussions with relatives. Objective In response to this challenge, we sought patient recommendations about how to improve genetic risk communication to enhance interfamilial discussions about primary and secondary disease prevention. Design We conducted 25 semi‐structured interviews with individuals who received genetic testing through British Columbia’s Hereditary Cancer Program between 2017 and 2018. Interviews were professionally transcribed and analysed using a constant comparative approach. Results Participants described difficulty engaging in conversations with relatives who were resistant to receiving genetic risk information, when communicating with younger relatives and where participants reported strained familial relationships. Participants recommended that testing facilities provide a summary of results and implications and that resources be made available to prepare patients for challenging discussions with family members. Discussion Our study demonstrates that individuals undergoing genetic testing for suspected hereditary cancer syndromes would benefit from additional supportive resources alongside genetic counselling. Providing this on‐going support will enhance the accurate and transparent communication of risk to facilitate the uptake of cascade testing and enhanced prevention strategies.


| INTRODUC TI ON
Genetic testing using next-generation sequencing technologies for the diagnosis of hereditary cancer syndromes is increasingly transitioning from research to clinical settings. The clinical application of multi-gene panels is intended to guide decisions about enhanced primary and secondary prevention strategies as well as genetics-informed treatment options. Due to the hereditary nature of certain cancer syndromes such as Lynch, Li-Fraumeni and hereditary breast and ovarian cancer syndromes, test results carry implications for the first tested individual in the family-probands-as well as their genetic family members. Communicating accurate genetic risk information allows potentially affected family members to undergo testing and-where appropriate-benefit from enhanced prevention strategies. [1][2][3][4][5] Current legislation within Canada and the United States does not require probands to discuss genetic test results with family members. 6 Due to privacy concerns, health-care providers are unable to contact probands' relatives directly. 1 While the communication of genetic test results to genetic relatives is not legally required, accurately relaying information about familial risk carry both personal and health systems implications. A wealth of evidence suggests that communicating genetic risk information is a complex process affected by both informational and interpersonal barriers and subjects to substantial individual variation. 2,[7][8][9][10][11][12][13][14][15] Patient-reported barriers to communication about genetic risk include informational complexity, motivation, family culture, as well as predicted and experienced familial reactions. 7,8,11,[16][17][18] In response to reported barriers, health-care providers offer strategies such as allocating genetic counselling time to addressing family dynamics, as well as the provision of family letters and testing facility contact information to relatives. 18,19 In addition, testing institutions provide guidance to encourage communication with potentially affected family members. 20,21 Despite such efforts, rates of cascade testing remain minimal, limiting the population benefit attributable to genetic testing for familial cancers. 12,22 Tested individuals are the vehicle by which information about hereditary cancer susceptibility is relayed to family members. For this reason, there exists an unmet need to determine how to enhance the communication process, from the perspectives of those who have undergone testing. To date, there is a lack of patient-directed guidance to mitigate challenges to communicating genetic risk to relatives. High-quality patient decision support techniques present an opportunity to enhance shared decision making and supplement genetic counselling sessions, but do not yet exist for the purposes of enhancing interfamilial communication about hereditary cancers. 23 to meet this overarching objective will help to ensure equitable access to prevention strategies for high-risk families.

| Objectives
The current study was initiated in response to an unmet need to identify patient-guided strategies to improve communication about hereditary cancer susceptibility. This work represents the preliminary phase of a larger investigation to develop a patient-values informed decision support technique for hereditary cancer susceptibility genetic testing. The qualitative work was conducted specifically to inform the content of the decision support tool in the form of an e-health application developed for feasible implementation.
Here, we report on the aspect of patient interviews that pertain to communicating genetic testing information to family members.

| Patient partner engagement
Our patient-oriented approach involved on-going consultation with a patient partner diagnosed with a hereditary cancer syndrome. Our patient partner was actively involved in protocol development, review of all study documentation, interview study design, interpretation of findings and review of research outputs. She attended all research team meetings either via teleconference or in-person.

| Interview guide development and piloting
The study team developed an interview guide to explore patient experiences with the process of genetic testing and communicating

| Participant eligibility and recruitment
Patients eligible for this study were 19 years or older, received carrier or index genetic test results between 2017 and 2018, had previously consented to be contacted for future research studies and were able to complete an interview in English. Index testing occurs when the proband is tested in the absence of a previously identified hereditary cancer syndrome in his or her family. Carrier testing is undertaken when a familial cancer syndrome has already been identified in the family, and typically, an asymptomatic individual is tested for the presence of known syndrome-specific pathogenic (disease causing) variants.
To maximize participation, two recruitment approaches were taken. First, we identified a list of individuals having recently undergone genetic testing and had provided written consent to be contacted for future research. Potentially eligible participants were identified through the Hereditary Cancer Program database.
Following the identification of eligible individuals, the study coordinator (SP) distributed a study invitation and consent letter via post. Non-responders were contacted via telephone to assess interest after two weeks. Second, one investigator (SS) approached eligible patients in clinic to ascertain interest in the study. The study coordinator followed up with individuals who expressed interest in participating. Investigators applied a maximum variation sampling technique to ensure diversity in age, sex and personal experience with cancer. Participant recruitment continued until two reviewers (SP and SK) agreed that data saturation had been achieved. were provided beyond information about her participation in the research project. All interviews were audio-recorded following written participant consent. The interviewer took minimal notes during the interview and documented field notes immediately following.

| Study process
For in-person interviews, only the interviewer and participant were present in the room. A distress protocol was maintained during each interview. 37 Participants completed a brief demographics questionnaire prior to each interview. Each participant was mailed an honorarium of CAD$75.00 following the interview.
All interview transcripts were professionally transcribed, de-identified and reviewed for accuracy prior to initiating the qualitative analysis. Transcripts and field notes were maintained on the

Selected semi-structured interview question Prompt (optional)
Decision-making process What kind of information do you think is important to have before deciding whether or not to have a genetic test?
Is there anything that you know now that you wish you had known before you made the decision? Which of these issues is the MOST important to you?
How do you think that information should be presented?
In person by a genetic counselor? Online?
Experience with the return of results research group's password-protected secured drive with access limited to researchers listed on the ethics approval. Interview transcripts were not returned to participants.
Two coders (SP and SK) applied a grounded theory approach to the qualitative analysis, using constant comparison for the development of the code book. 38 Analytic codes were identified inductively to ensure that major themes emerged from the data rather than through a priori expectations. Interviews were coded in batches of two using QSR International's NVivo 12 qualitative data analysis software. 39 Coders discussed in vivo codes after each reviewing two transcribed interviews, identifying areas of disagreement and revising the code book accordingly. This process continued until both coders were satisfied with their agreement and the code book. SP revised and maintained the code book throughout the iterative process of interviewing and analysis. To ensure consistency, reviewers coded 30% of the interview transcripts independently and in duplicate. SP coded the remaining interviews. Themes that arose through the analytic process were not verified by interview participants. reported the return of a variant of unknown significance or an inconclusive finding (see Table 2).

| Summar y of major themes
Interview participants described a variety of experiences communicating genetic risk to family members. Communication challenges were highly contextualized given initial attempts at discussions about test results, relatives' perceptions about cancer risk, the presence of a family history of cancer, family culture, and interpersonal relationships with relatives. Here, we report barriers and facilitators identified through the qualitative synthesis, followed by a discussion of participant recommendations for facilitating constructive risk communication (Table 3).

| Family culture and interpersonal relationships
Interpersonal  Participants who experienced strained conversations with close family members struggled with the decision to inform second-degree relatives. In two specific conversations (quotes 12 and 13), participants expressed a lack of clarity about the duty to inform family members. Although the duty to inform was discussed in a small subset of interviews, the topic was met with substantial distress and confusion regarding who should be informed, and how discussions with resistant family members should be broached. Participants whose attempts to relay genetic risk information were stonewalled by resistant family members expressed considerable frustration.

| Family history of cancer
The presence of a known family history of cancer served to both facilitate and stifle constructive conversations. As shown in quotes

| Par ticipant recommendations
Following discussions about communicating genetic risk to family members, participants discussed ways in which an adjunct to genetic counselling could improve this process. Recommendations were not framed specifically in relation to the potential for an e-health app.
Rather, participants discussed recommendations in terms of broad strategies that would support the process of communication (quotes [18][19][20][21][22][23] Communicating with young relatives 5 "I have two sons, grown-up sons with children of their own. And I told them. It was hard to tell them…I remember myself at their age. Things like that meant nothing to me…" (014) 6 "I don't know how seriously they take it. You know, even with the melanoma…I'm always going on about sunscreen, and being careful and wearing hats, and… I don't think they pay that much attention or take it that seriously… I find that, you know, that's the thing about young people thinking they're infallible perhaps'. (018)

13
"So my brother's wife was a little resistant. She was like, "If you have it I'm not telling my daughters…I don't want to start freaking them out for the future." But to me that was a poor decision, but I guess that leads to some other moral issues. Do you go behind their backs and tell their daughter…?' (006) Familiarity with discussing cancer 14 "She's always known, all along, you know, that this may be passed on, and that we will end up having this discussion". (017) 15 "I was in touch with the other [siblings] as I was having the testing done, and I said, "This could --you know, you could possibly --if this test comes back positive, there is an option that you guys could be tested and see if it stops here." And they were all onboard with that. None of them didn't want to know. They all wanted to know so that they could take possible actions to stop it. And two of my siblings have female offspring, and they're worried about them having the breast cancer factors. And so they're going through the testing right now. And I was informed that if it's negative for them, then it doesn't go past that generation". (002)

16
"That's maybe one of the sad parts, when there's enough people in the family that have had cancer that --I guess they sort of accept it as a reality that, you know, the likelihood of people getting cancer is quite high. So they're sort of familiar with the process". (015)

17
It was a little challenging initially just telling my parents, because both of them didn't want it to be from them. So, there was a bit of tension. And a little bit of guilt from both of them, and that was really tough. 009 confidence about how to accurately relay the information in a manner that would be sensitive to the potential for worry, upset or guilt (quote 18). A key feature of participant recommendations was to better prepare probands for resistant family members and to provide them with the ability to manage negative reactions. Participants sought resources to prepare them for potentially difficult discussions, as well as on-going support following unsuccessful attempts at communication (Table 4).

| Limitations
The results of this work should be interpreted alongside limitations.
Firstly, responses to the interview were self-reported and therefore Finally, our sample consisted of participants who had previously consented to be contacted for future research. The subset of individuals interested in research participation may differ systematically from the total population who underwent genetic testing. Despite the potential for selection bias, we sought to ensure a diversity of perspectives and experiences were captured, and recruitment continued until thematic saturation was reached. Qualitative research studies such as this do not seek sample representativeness and generalizability of findings. Given the diversity of communication experiences captured in this interview study, we are able to report on a substantial heterogeneity of experiences and challenges communicating genetic information to family.

| CON CLUS IONS
Successful communication between probands and their family members is a highly individualized experience informed by multiple interpersonal factors. Our findings support the development of improved resources to assist patients through the entire trajectory of genetic testing. This on-going support will ensure patients have the motivation, self-efficacy, and informational resources for successful communication with their families. We further identify a need for practical guidance about how to broach conversations, and how to manage family dynamics when discussions are unsuccessful.
While genetic counsellors have a responsibility to provide patients with adequate information that prepares them for constructive risk communication, they are facing time constraints in publicly funded health-care systems. Additional supports that reduce genetic counsellor burden and enhance the familial communication process will better enable cascade testing programmes to benefit at-risk families.

ACK N OWLED G EM ENTS
The authors gratefully acknowledge the valuable contribution of our patient partner, Chiquita Hessels.