The experience of receiving a letter from a cancer genetics clinic about risk for hereditary cancer

Direct contact may be an option for supporting risk disclosure in families with hereditary cancer. In this qualitative interview studywe explore how healthy at-risk relatives experience receiving a letter with information about hereditary cancer directly from healthcare. The study is part of an ongoing multicentre randomised clinical trial in Sweden that evaluates the effectiveness of direct letters from cancer genetics clinics to at-risk relatives (ClinTrial NTC04197856). We invited 14 relatives who had received a letter and contacted the clinic. We did semi-structed interviews and analysed the data with thematic analysis. The participants had different levels of prior knowledge of the hereditary cancer assessment and many but not all knew that a letter was coming. Overall, these participants believed healthcare-mediated disclosure could complement family-mediated disclosure. They expressed that the letter and the message raised concerns and a need for counselling. they wanted healthcare to be accessible and informed when taking contact. The participants found the message easier to cope with when they had been noti�ed by a family member on forehand, a general attitude was that notifying one’s relatives was a decent thing to do. They thought healthcare should help patients in the disclosing process and also guard the relatives right to be informed. This study supports a direct approach from healthcare as a possible complement to the established model of family-mediated risk disclosure, however further research is needed to develop a good practice.


Introduction
Both patients and their at-risk relatives have an interest in the results of genetic testing for hereditary cancer.Identifying high risk of hereditary cancer such as breast-and ovarian cancer syndrome (HBOC) or Lynch syndrome is important for the affected individual because it sets the stage for targeted prevention programs, including risk reducing surgery, that reduce both cancer incidence and mortality (1,2,3,4).
Once healthy at-risk relatives are identi ed as a carrier of a familial variant of a cancer predisposing gene, they can be offered such a prevention program.Also, individuals in families with a high occurrence of colorectal cancer but a negative genetic screening can be offered effective prevention programs (5).
Clinical practice in Sweden and Europe, USA and also Australia, advocates for family-mediated disclosure.That is, the genetic healthcare professional is responsible for counselling the patient about their responsibility to inform their relatives.This ethically and legally well-established approach can be disputed as established counselling practices are changing.The indications for genetic testing have been extended, there is a steady increase in the number of patients and families that has to be counselled, with limited healthcare resources, both at cancer genetic clinics but also by non-genetic healthcare professionals such as oncologists and surgeons, so called mainstream testing.Further, we also argue that healthcare has a responsibility to ensure that information is made available to at-risk relatives (6).
One recent meta-analysis, which compiled evidence of current established practice of family-mediated disclosure, reported that about 70% (95% CI 60-78%) of at-risk relatives are informed about hereditary risk.Of these, about 43% (95% CI 27-61%) undergo genetic testing for the familial variant (7).Another meta-analysis on hereditary cancer risk disclosure shows that with family-mediated disclosure the uptake of genetic counselling in relatives is about 35%, whereas the uptake almost doubled (63%) when using a direct contact approach (8).
However the attitudes and reactions of the at-risk relatives to such direct contact and potentially unsolicited disclosure by healthcare is not well known.A handful of studies with data from both questionnaires and interview studies show that at-risk relatives perceived it as an acceptable but also complicated complement (9,10,11) This study is performed in the context of an ongoing Swedish multi-centre randomised clinical trial (12) evaluating whether the offer of direct letters to at-risk relatives regarding hereditary cancer impacts the rate of relatives contacting Swedish cancer genetics clinics.In this qualitative interview study, we explore how at-risk relatives experience receiving a direct letter from healthcare.More speci cally we explore how the participant reacted to having a letter and what their attitudes are toward healthcare-mediated risk disclosure.

Study design, data collection and analysis
We performed a qualitative exploratory interview study where the participants were at-risk relatives who had received a direct letter from a cancer genetics clinic.We sent the letter, adjusted to the familial risk and the gender of the recipient, as an intervention in a Swedish clinical randomized controlled trial that compared the letter intervention to standard care.All letters disclosed hereditary risk information, offered genetic counselling and testing.For details of the letters, see preprint study protocol of the DIRECT-study (12).When a relative contacted the cancer genetics clinic a genetic counsellor invited them to participate in the study and we scheduled an interview within two weeks of the contact.The sampling was both purposive and convenient.The rst author conducted the interviews using an interview guide based on the research questions, existing litterature and our own expertise in clinical cancer genetics.The interviews were recorded and transcribed verbatim, lasting between 21 and 50 minutes.The rst interview was in person, however because of the Covid-19 pandemic, two of the interviews were conducted via video and eleven via telephone.
In total, we did 14 interviews between September 2020 and April 2022.When being interviewed, all the participants had received some basic counselling from a genetic counsellor via the telephone, some were also waiting for a scheduled appointment, none had provided a blood sample or received their predictive genetic test results.
The rst author read the transcripts, noted impressions, and coded the text using the software program OpenCode 4.03 (13).We analysed the codes for similarities and differences and grouped them into subthemes and themes using thematic maps.Descriptive results was formed from manifest codes and the thematic results from both manifest and latent codes.We did the analysis with an inductive and re exive thematic approach as presented by Braun and Clark (14, 15, 16).The authors -all clinicians with experience in clinical cancer genetics, genetic counselling, and oncology -continually discussed the data, cross-checking transcripts and codes and developing themes.
Although the qualitative results should be seen as a thematic interpretation of the interviews, with no attempt to look for representativity in terms of number, we use the terms 'some' when 2-7 participants expressed a certain thought or feeling, 'many' for 8-11 participants, and 'most' for 12-13 participants.We do this to facilitate understanding of the data.

Ethical consideration
This study was approved by the Swedish National Ethical Review Board (application no 2019-02647 and 2020 − 01176).All participants signed an informed consent.

Results
Participants' characteristics are found in table 1.We present both descriptive and thematic results: i) a description of the manifest content of participants' actions and reactions when receiving the letter, and ii) themes developed when analysing the transcripts with thematic analysis searching for experiences and attitudes.

i) Actions and reactions when receiving the letter
All participants found it easy to understand the letter's language and content and most found the contact information to be complete.They also found it helpful that the letter contained the relative's name or a family-related serial number.When the participants received the letter they had varying degrees of prior knowledge about the familial cancer genetics assessment.Many participants had been informed to some degree about the assessment and that a letter was coming.
For some participants the letter arrived without any forewarning.Two of these had a rst-degree relative with a cancer diagnosis associated with a hereditary cancer syndrome.One participant found that the letter made sense as she had been thinking about heredity for cancer in the family.Another participant did not have any prior knowledge of cancer in the family and described the letter evoking many questions about her extended family, the risk for cancer, and how the information was presented in the letter.Of those without prior knowledge most but not all contacted a relative for more information.
After receiving the letter many called the clinic within days or a few weeks, but some waited up to a couple of months.Those who immediately responded to the letter explained their action as a result of wanting to ask the counsellor clarifying questions and to provide a blood sample.Those who delayed responding to the letter explained the delay as the result of other life events such as the Covid-19 pandemic, the birth of a child, or caring for an ill parent.A few described that they wanted to contact but that it just didn't happen which could be interpreted as feelings of resistance, and one participant mentioned feelings of guilt towards the family.
Many expressed a need for genetic counselling before telling their own family members about the letter, some even wanted to know their own test result rst.At the time of the interview, about half of the participants had told at least one close relative (a partner, a co-parent, a sibling, or an adult child) about the letter, but they had not necessarily informed all family members in their turn affected by the information.Some did not have a relative who needed disclosure.Two had not disclosed the information at all.
ii) An important message to hold and to handle for oneself and for others When analysing the interviews regarding the experience of receiving a direct letter and the attitudes toward disclosing hereditary cancer risk, we developed an overarching theme and six subthemes (Figure 1).
The overarching theme -An important message to hold and to handle for oneself and for otherssummarizes that the message of hereditary risk and the letter, had to be dealt with.The impact of the very letter itself depended on if and how much the participants were previously informed by their relatives, being informed helped them cope better.The message evoked mixed feelings in the participants and ambivalence between the bene ts of accessing risk control but also, to some degree, the drawback of knowledge causing worry.They had to process what the letter or message could mean, or bring, for themselves and also for their children, co-parents or grandchildren.They were thinking and worrying about how and when to pass on the information to their relatives in turn.They also clearly expressed that disclosing is a family matter, however healthcare should support both patients and relatives when necessary.
One might need to kind of, digest it a little bit . . ."How should I think about it?What do I think of it?Do I want to know?How do I want to proceed?" (Male participant, family with HBOC) It felt important, worrying or even frightening.
Those who had been noti ed about the letter on forehand expressed that the letter was important but also concerning.Some had been waiting for the letter.Others described it as an unpleasant reminder of what they already knew or that it made them worried about their and their children's futures: Even The participants who had not known a letter was coming described feeling confused, worried and even fearful when reading the letter.They described this unsolicited message as di cult to take in and to understand and that the letter raised questions.Two participants did not question the approach of sending a letter but expressed some doubt as they described that their partners questioned the appropriateness of the approach.
I just got the Corona vaccine, a kind of ticket [back to normality] and now I get a letter, a new ticket to an insecure future.(Female participant, family with Lynch syndrome)

I want access and understanding when contacting
Most of the participants out a need for concise information in the letter regarding who and where to call.They expressed that they wanted, expected, or even demanded to have their self-initiated contact call answered promptly.When presenting themselves and their case, they wanted the counsellor to be informed and familiar with genetic assessments, the direct letter, and preferably also their own family.
They wanted to have counselling on the phone or schedule an appointment for counselling and genetic testing, as the following notes indicate: I did think she [my mother's counsellor] would answer but then it wasn't her, and then I had to answer the kind of questions I had hoped not to.I wished it would've been her who knew my mum [. ..] but it went well.(Female participant, family with HBOC) Talking to the counsellor was mostly described as positive and reassuring.However, being counselled over the phone directly when contacting the clinic was sometimes described as concerning and overwhelming.
A personal notice from relatives is welcomed and the right thing to do Participants without prior knowledge spontaneously expressed disappointment or anger with relatives who did not notify them that the letter was coming.The participants who had been informed about the assessment and the letter appreciated the personal notice even if brief and from a more distant relation.It was a general attitude among participants that it was caring or even correct or decent to personally notify relatives about the familial assessment before healthcare-mediated disclosure.
They could've called us and told us that [the index relative] is having a [cancer genetic] assessment and that it means that we also will have to do it.It's a bit. ..I feel a little dis. . .I feel disappointed and slightly angry.For heaven's sake, we don't have the best family relations, but when it comes to life or death like this, one thinks that . . .well. . .she has to get a hold of herself.(Female participant, family with HBOC)

Disclosure is a family matter by constitution
All the participants talked about the responsibility of disclosing to relatives as a family matter without re ecting on this point.Some expressed their attitude in a more direct way -e.g., making this information available to relatives is a duty: One can draw parallels to Covid and vaccine . . the right to decide for yourself what you want do and what info to take in and how to live, but there must be some responsibility towards others [relatives and people in general] or at least respect for others . . .one is part of something greater.participant, family with Lynch syndrome) They expressed concern about their own and their relatives' risk.They considered the act of disclosing to be something that needed to be well thought out and done in a responsible and caring way.Their own plans for disclosure ranged from rehearsing what they would say, waiting for a family gathering to tell in person, to waiting for their own test results to avoid unnecessary worry.Interestingly, no participant addressed the possibility to ask the cancer genetics clinic to send letters to their relatives in turn.
Healthcare should support the family but also guard the right of the individual All participants assumed that patients receive support from healthcare professionals during an assessment for hereditary cancer.They thought that patients might need extra support as they may not understand the information or why it is important to disclose.They could also imagine the patient not feeling comfortable approaching relatives, not capable due to their illness or that they did not want to reveal their own diagnosis.All thought healthcare should contact relatives directly if patient asked for help or if there was a concern disclosing not take place: Healthcare must take responsibility and reach closure even if the patient who started the isn't coping, healthcare has to support and reach closure.(Male family with HBOC ) . . .but it's not that person's own business anymore if it's something that can be passed on in the family.
(Female participant, family with Lynch syndrome) Some that a patient should not have the right to withhold information from biological However one participant wanting the right to have cient time to inform relatives himself before healthcare did.Another participant suggested that knowing a letter was on its way would be a reminder to the patient to notify distant relatives.

An unsolicited letter can safeguard autonomy but may harm
The participants thought that healthcare should send direct letter to relatives to safeguard the individual's autonomy and agency.These at-risk relatives believed they had the right to know about their risk.That is, if a counsellor understands that the patient might fail to inform, a letter was an appropriate measure to take.In general, these participants trusted healthcare and perceived targeted prevention programs to be bene cial.
However, some participants expressed ambivalence towards direct contact, the role of healthcare in society, and the effect of targeted prevention programs.They expressed concern that direct contact might be seen as offensive or a breach of privacy and that surveillance might impair one's perception of being or feeling healthy.In addition, they expressed concern that prevention programs cannot prevent cancer but only offer early detection and that such a program introduces a risk of overdiagnosing.Some re ected on the fundamental uncertainty of life and the illusion of having control.
I feel lika a fairly stable person but [. ..] a person who [. ..] maybe has a depression or something, getting a letter like this can be terrible.Also what you don't know you cannot control but you don't have to worry about it either.(Female participant, family with Lynch syndrome) Both those with and without prior knowledge of when they received the letter, commented on the possible negative impact of the unsolicited risk disclosure.If a person who received letter was in a di cult life situation or had limited resources to handle the message, it could be misinterpreted or overinterpreted and therefore could do harm.One commented on an adult sibling needing emotional support from family after being informed.Some noted that some people who receive this kind of letter could choose to not make contact, so there had to a plan and to follow-up on who receive a noti cation letter.

Discussion
The practice of family-mediated risk disclosure of hereditary cancer is well established at cancer genetics clinics.As the use of genetic testing broadens and the number of patients increases the limitations regarding e ciency in reaching at-risk relatives must be addressed.Previous meta-analysis indicates that it might be reasonable to consider implementing a practice for a healthcare-mediated direct approach (8).In this study, we explored experiences and attitudes of at-risk relatives being exposed to such a direct approach of risk disclosure by letter within the context of a trial in a clinical setting.
Most participants in our study found it acceptable to receive a direct letter, because they expected it or because they found the information important.These results are in line with qualitative data from a Danish follow-up study showing that at-risk relatives who experienced an unsolicited and direct letter about Lynch syndrome found the information both relevant and important (11).
Further, In Lynch family members approached by a noti cation letter, 76% of Danish participants (11) and 91% of Finnish participants (10) thought it was generally acceptable to be noti ed about hereditary cancer risk by letter.
The participants who had prior knowledge of the familial assessment and the letter coming expressed that it helped them cope with the situation.Without prior knowledge it was more complicated as the letter evoked negative feelings and a need for more counselling.After receiving a letter the participants expected a professional handling of their case when contacting the cancer genetics clinic.It is a reasonable demand that if health care take the initiative to reach out to relatives directly, they also have an increased responsibility regarding access to care and follow-up for those they have approached.
It was a recurrent theme that participants wanted a personal notice from their relatives before healthcaremediated disclosure i.e., before receiving a letter, and they wanted to inform their own relatives who were in turn to be noti ed, and this was perceived as the decent thing to do.In contrast in the Danish study of direct contact, only half of the relatives (49%) thought it was important to be noti ed about the letter before receiving it (11).
Regarding attitudes towards direct risk disclosure from healthcare the participants expressed that heredity is a family matter and relations matter, disclosing had to be done in a responsible and caring way.At the same time, participants approved of a direct approach from healthcare as they believed healthcare is obligated to help patients with disclosure and safeguard the rights of relatives.We found it interesting that our participants re ected on how and when to inform their relatives but even though they themselves had received a letter, they did not spontaneously mention a direct approach as an option.Some participants expressed concerns, directly or indirectly, on the possibly negative or even harmful aspect of receiving an unsolicited letter from healthcare.According to questionnaire data from the Lynch syndrome cohort of relatives, 3% of those receiving a direct letter would have preferred not to have this information at all (11).Studies quantifying the emotional effect of direct approach are scarce but point measurements of STAI (state trait anxiety index) in relatives receiving a noti cation letter indicate that the psychological consequence is similar to the family-mediated approach (9,10).However, as the information on risk may have lifelong implications it would be interesting to investigate long-term understanding and coping for relatives reached by an unsolicited direct approach.
A strength of this qualitative study is that the participants recruited have a real-life experience of direct contact.The interviews were conducted within two weeks of the participant contacting healthcare in an effort to capture the experience of receiving the letter in clodse proximity in time.However, a possible limitation is that the counsellor answering the call and inviting the participant to an interview also answered questions and gave some counselling that could have in uenced the participants' experience of being approached.
A limitation to our study is that we do not cover the experiences of relatives who did not approve of being approached with a direct letter and did not contact healthcare, nor can this kind of data be found in previous studies to our knowledge.We nd our own and others' results compatible with the suggestion of a clinical approach where healthcare professionals experienced in genetic counselling can consider disclosing risk by a direct letter to at-risk relatives.The approach applies to clinically relevant risks, herein high risk of hereditary cancer where healthcare offers target prevention programs.Direct contact should be a complement to the established approach of family-mediated disclosure and as it is ethically complex it needs to be tailored for the individual patient and his or her family in the clinical situation.Also country-speci c boundaries may limit the use of a direct letters.
Further research is necessary to establish a good practice for healthcare reaching out directly to relatives.Such a practice preferably includes guidelines on when and to whom information is relevant and when and to whom healthcare could and should make direct contact.

Figures
Figures

Figure 1
Figure 1 if I knew it [the letter] was coming, it did hurt a little bit when I got it […] it affects you, it does, I'm telling you that.(Male participant, family with HBOC) When I got the letter, had dad not told me earlier, I wouldn't have wanted such a letter as it was.(Male participant, family with HBOC) I think the letter is a good thing.I don't like getting it, but I think . . .like . . .it's good . . .like . . .that I got the possibility to know.(Male participant, family with HBOC) Declarations 11.Petersen HV, Frederiksen BL, Lautrup CK, Lindberg LJ, Ladelund S, Nilbert M. Unsolicited information letters to increase awareness of Lynch syndrome and familial colorectal cancer: reactions and attitudes.Fam Cancer.2019;18(1):43-51.12. Hawranek C, Ehrencrona H, Öfverholm A, Numan Hellquist B, Rosén A. Direct letters to relatives at risk of hereditary cancer -study protocol for a multi-centre randomised controlled trial of healthcareassisted versus family-mediated risk disclosure at Swedish cancer genetics clinics (DIRECT-study), 26 April 2023, PREPRINT (Version 1)2023.13.Health ISaSDaDoEaG.OpenCode 4.0.https://www.umu.se/en/department-of-epidemiology-andglobal-health/research/open-code2/:University of Umeå, Sweden.; 2011.14.Braun V, Clarke V. Re ecting on re exive thematic analysis.Qualitative Research in Sport, Exercise and Health.2019;11(4):589-97.15.Braun V, Clarke V.One size ts all?What counts as quality practice in (re exive) thematic analysis?Qualitative Research in Psychology.2020;18(3):328-52. 1 .Braun V, Clarke V. Using thematic analysis in psychology.Qualitative Research in Psychology.
TableTable 1 is available in the Supplementary Files section.