“I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants

Abstract

Little is known about what uncertainties patients experience after being identified to carry a pathogenic variant in a moderate-risk cancer gene as a result of undergoing multigene panel testing for cancer susceptibility. Data regarding cancer risk estimates and effectiveness of risk management strategies for these variants continues to evolve, which has the potential to evoke uncertainty. Acknowledging uncertainty during pre- and post-test discussions is imperative to helping individuals to adapt to their results. A better understanding of this population’s experience of uncertainty is needed to facilitate such discussions and is the aim of the current study. Semi-structured interviews (30–60 min in length), informed by Han and colleagues’ taxonomy of uncertainty in clinical genomic sequencing, were conducted to assess motivations to pursue genetic testing, areas of perceived uncertainty, and strategies for managing uncertainty among 20 carriers of pathogenic variants in two moderate-risk genes, ATM and CHEK2. We found that participants pursue genetic testing with the expectation that results will clarify cancer risks and approaches to management. Participants experience uncertainties aligning with Han’s taxonomy relating to the ambiguity of specific cancer risk estimates and effectiveness of certain risk management strategies. These uncertainties influenced decisions around the uptake of risk management strategies, which were additionally impacted by clinicians’ uncertainty towards such strategies. Participants employ a variety of uncertainty management approaches to cope with their anxieties. Clinicians may wish to use these findings to facilitate patient adaptation to the implications of multigene panel testing for cancer susceptibility during both pre- and post-test counseling sessions.

Introduction

Multigene panel testing allows for an efficient approach to determine a potential genetic cause for inherited cancer susceptibility [1]. However, the clinical utility of such testing remains in question as many genes included on panels are moderate-risk genes with less established data on cancer risk estimates and risk management [2, 3]. Two examples of moderate-risk genes are ATM and CHEK2. The highest cancer risk associated with these genes is breast cancer, with an estimated lifetime risk of 33% for ATM and 28–37% for CHEK2, which is considered ‘moderate-risk’ compared to the higher lifetime breast cancer risk associated with BRCA1 (60%) and BRCA2 (55%) [4,5,6]. However, less is known about the cancer risks and appropriate management for moderate-risk genes in comparison to genes such as BRCA1/2, perhaps due to differences in how long clinical testing has been available for them: BRCA1/2 since 1996 and multigene panel testing within cancer genetics since 2013 [7].

Quantitative studies investigating patient outcomes after undergoing multigene panel testing for cancer susceptibility demonstrated increased levels of anxiety and uncertainty in those who test positive for a pathogenic variant [1, 8, 9]. Other studies have found that uncertainty and anxiety are not predominant feelings among individuals who pursue genetic testing for cancer susceptibility, and that in fact, learning about cancer risk provides individuals with an opportunistic sense to be more proactive about their healthcare [10,11,12]. However, a majority of these studies are limited in that they examine levels of psychological distress and health outcomes for individuals who are from high-risk breast cancer families who undergo BRCA1/2 testing only. Thus, these results should not be extrapolated to impute the views of those who carry moderate-risk variants. One study found that carriers of pathogenic variants in moderate-risk cancer genes experienced higher levels of uncertainty with regard to cancer risk and decision-making about cancer screening compared to carriers of pathogenic variants in high-risk cancer genes, such as those found in BRCA1/2 [13]. It has been hypothesized that the uncertainty experienced by these moderate-risk variant carriers may be due to limited empirical data around cancer risk estimates and the effectiveness of risk management strategies for moderate-risk cancer genes [3, 13, 14].

Limited empirical data around cancer risk estimates and the effectiveness of risk management strategies for moderate-risk cancer genes has the potential to evoke uncertainty in individuals who carry pathogenic variants within these genes. These limitations are reflected in the current data around cancer risk and management for ATM and CHEK2. For example, although the National Comprehensive Cancer Network (NCCN) in the U.S. has an established recommendation for carriers of pathogenic ATM/CHEK2 variants to undergo annual mammogram with consideration of tomosynthesis and breast MRI with contrast starting at age 40, the NCCN recognizes that evidence for risk-reducing mastectomy is insufficient for these carriers and advises clinicians to manage breast cancer risk based on family history [15]. Additionally, the effectiveness of breast cancer risk-reducing strategies, including chemoprevention, for carriers of these variants is not yet known [16, 17].

Beyond breast cancer, the risks conferred by pathogenic ATM and CHEK2 variants for other cancers remains unclear. For example, ATM has been associated with ovarian, pancreatic and prostate cancer, but the degree of risk to develop these cancers for unaffected carriers remains unclear [18,19,20]. The NCCN guidelines at the time of this study state that while there is a potential increase in ovarian cancer risk for carriers of pathogenic ATM variants, there is insufficient evidence to recommend risk-reducing salpingo-oophorectomy. Additionally, current guidelines do not recommend increased prostate cancer screening for ATM carriers, and recommendations for increased pancreatic cancer screening remain complex and are often based on family history [15]. Similarly, colorectal cancer risk data and screening guidelines for individuals who have a pathogenic CHEK2 variant continue to evolve, with current guidelines recommending earlier colonoscopy screening than the general population [21]. At this time, many different variants have been identified within ATM and CHEK2 and genotype–phenotype correlations continue to evolve; current NCCN guidelines do not differentiate care based on the type of variant within the particular gene. Consequently, the appropriateness of recommended risk management strategies prescribed to carriers of pathogenic variants in either gene remain unclear.

The evolving risk estimates and management options for ATM and CHEK2 have the potential to increase uncertainty for patients. The only way to avoid such uncertainty would be not to test for these genes, which may give rise to other harms, such as an inability to be proactive with cancer screening for those who remain unaware of their increased risk. Understanding and managing uncertainty, both prior and subsequent to testing (or a decision not to test), is therefore vital to helping patients manage their health. However, little is known about the patient experience of uncertainty when undergoing multigene panel testing for cancer susceptibility and no studies to date have attempted to characterize the uncertainty experienced by carriers of pathogenic variants in either ATM or CHEK2 [22].

Han and colleagues developed a conceptual taxonomy to assess the unique uncertainties seen in the context of clinical genetic testing [23] (summarized in Table 1). The taxonomy (hereafter referred to as “Han’s taxonomy”) defines uncertainty as “the conscious awareness of ignorance—a self-awareness of incomplete knowledge of some aspect of the world.” Han’s taxonomy divides uncertainty among three major dimensions: source, issue and locus. Source refers to the cause or etiology of a given uncertainty. Types of sources include indeterminacy of future outcomes, such as the probability of developing cancer, as well as imprecise or conflicting information. Issue refers to “the specific substantive matter about which an individual lacks knowledge”, or implications of uncertainty. For example, the strength of cancer risk data for a gene may impact the perceived appropriateness of engaging in cancer risk management strategies. Lastly, locus describes within whose mind uncertainty resides. This can include the patient, clinicians, patients’ family members, payers or healthcare policy makers.

Table 1 Summary of the three major dimensions of Han and colleagues’ taxonomy of uncertainty in clinical genome sequencing

In-depth qualitative analysis is needed to fully appreciate the subjective perception of uncertainty. Previous qualitative studies have examined the uncertainty experienced by high-risk variant carriers, notably within BRCA1/2, and found causes of uncertainty related to conceptualization of cancer risks and unclear benefits of participating in screening procedures [24,25,26]. In the context of the increased use of multigene panel testing for cancer susceptibility and thus the increased identification of carriers of pathogenic ATM and CHEK2 variants, a better understanding of how these individuals experience and reflect on uncertainty is necessary in order to promote patient adaptation (i.e. increase understanding and adaptive emotional coping, promote values-based decision making and constructive health behaviors) to the implications of such testing. Thus, the aim of the current study was to characterize the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants using Han’s taxonomy.

Methods

Participants

The target study population was individuals who have a pathogenic or likely pathogenic variant (hereafter referred to as a “pathogenic variant”) in ATM and/or CHEK2, both moderate-risk cancer genes. Participants were required to be 18 years or older at the time of the study, and able to complete an interview in English. As those affected by cancer may experience uncertainty differently from those who are unaffected, we excluded participants with a current or past cancer diagnosis in order to enhance the possibility of achieving data saturation in the sample. The studies involving human participants were reviewed and approved by the Stanford University Institutional Review Board. Participants reviewed an information sheet prior to completing the demographic survey and provided oral consent at the start of the interview. A waiver of written documentation of informed consent was granted, given the minimal risk of the study.

One hundred and one individuals who met the inclusion criteria were found in the Stanford Cancer Genetics Research Database between January 2014 and June 2019. Thirty-seven individuals agreed to have the demographic survey sent to them via email, of which 26 individuals responded (~ 70%). One respondent indicated they did not want to participate in the study, thus their answers to the survey questions were not included in the analysis. Three respondents were excluded due to a personal cancer diagnosis made since their information was collected for the database. Data saturation was reached after the 15th interview, however, to verify collected data and ensure a homogeneous group of perspectives, 20 interviews were conducted, ranging in length from 30 to 60 min. Thus, two of the remaining eligible participants were not interviewed.

Sampling

Participants were enrolled in the Stanford Cancer Genetics Research Database (Stanford University IRB protocol #12234). This database stores information, including past and current medical information (i.e. cancer diagnosis and treatment at the time of initial data collection), family history, and laboratory tests and results (including genetic tests), from patients who are seen in the Stanford Cancer Genetics clinic and have given consent to be recontacted for research purposes.

Individuals from the database who met the above inclusion criteria were contacted via telephone to offer recruitment into the current study. They were asked to review a participant information document and complete a demographic survey (collecting age, gender, ethnicity, personal and family history of cancer and contact information), sent to them via email. Participants were selected from those who completed the demographic survey to achieve a sample with a close to equal number of pathogenic ATM variant carriers and pathogenic CHEK2 variant carriers who also represented different age groups. The gender identity of the interviewees (80% female) was proportionate to that of the population who met the above inclusion criteria (79% female).

Instrument development

A semi-structured interview guide was developed by the research team, which consisted of genetic counselors with experience in a cancer setting (KGR, CC, MG), and bioethics researchers (KEO, AJN) with experience in uncertainty research, one of whom was also a genetic counselor (KEO). Questions were developed deductively using Han’s taxonomy of uncertainty to specifically ask about the source, issue, and locus of participants’ uncertainty without naming them as such (Supplemental File 1). Han’s taxonomy was perceived by the authors to effectively delineate the uncertainties experienced by individuals undergoing clinical genomic sequencing. As such, it was chosen as a deductive framework to characterize and describe the uncertainties experienced by participants in the current study. Additional questions were also developed that did not draw on Han’s taxonomy. These assessed participants’ motivations to pursue genetic testing and how they managed the uncertainty that arose from their genetic test results.

Data collection

Interviews were conducted in October 2019 by a single interviewer (KGR) using Zoom conferencing software, using only the audio function. Participants reviewed an information sheet about the study before the start of the interview. All interviews were recorded and transcribed verbatim, omitting identifiable information. Participants who completed an interview were provided a $20 Amazon.com gift card.

Data analysis

A thematic analysis approach was used throughout the data analysis process [27]. Data saturation was determined during the analysis process and defined as the point in which new data became redundant of already collected data (i.e. the same comments were being heard during subsequent interviews or read in transcripts) [28]. Coding occurred concurrently with interviews. A preliminary codebook was inductively developed by a single investigator (KGR) using eight interview transcripts [29]. The codebook was applied to one transcript at a time by multiple coders (KGR, CC, MG and KEO). Inconsistencies in code application were resolved by discussion. Five rounds of application and adjudication on five separate transcripts were performed until a final codebook was established. Team-based analysis is a recognized approach for generating codes in qualitative research, as multiple coders are thought to facilitate reliable and valid utilization of the codes [30, 31]. Once the codebook was finalized, interview transcripts were coded by a single investigator (KGR) using Dedoose (Version 8.2.14, 2019), an online analytic software program. To assure standardized use of the final codebook, three inter-rater reliability tests, comprised of 25–35 sample excerpts per test, were administered by a single investigator (KGR) throughout the coding process to another coder (CC). This resulted in a pooled kappa score ranging from 0.81 to 0.95 (very good agreement). Assessing inter-rater reliability on a sample of texts is an acceptable method to validate the reproducibility of code application amongst coders [32].

Once coding was completed, excerpts from each code were examined by a single investigator (KGR). Codes were organized into categories based on patterns (i.e. how often a code was used in conjunction with other codes) identified from the excerpts. Preliminary themes were derived by a single investigator (KGR) by highlighting and making notes in the margins of the excerpts from each code within each category. The entire research team discussed the preliminary themes and reached consensus on final themes.

Results

Demographic information for the 20 interviewees can be found in Table 2. Participants ranged in age from 28 to 77 years. The majority of the participants were female, identified as white, and had a high level of education. Nine participants tested positive for a pathogenic variant in ATM (ATM +), 8 participants tested positive for a pathogenic variant in CHEK2 (CHEK2 +), and 3 participants harbored pathogenic variants in both genes (ATM + and CHEK2 +). Participants’ family history information can be found in Supplemental File 2.

Table 2 Demographics

Three major themes related to the uncertainty experienced by our participants emerged from the analysis of the interview transcripts: Theme 1: Motivations to pursue genetic testing, Theme 2: Expressions of uncertainty, and Theme 3: Uncertainty management.

Theme 2, Expressions of uncertainty, consists of 6 subthemes including Subtheme 1: Receiving a result in an unfamiliar gene, and 5 additional subthemes that directly map to Han’s taxonomy (Table 3): Subtheme 2 (Source): Probability of developing cancer, Subtheme 3 (Source): Ambiguous cancer risk data, Subtheme 4 (Source): Ambiguous data regarding the effectiveness of cancer risk management strategies, Subtheme 5 (Issue): Ambiguity influences decisions about uptake of cancer risk management strategies, and Subtheme 6 (Locus): Clinician uncertainty towards management recommendations.

Table 3 Mapping uncertainty back to the Han et al. taxonomy

Theme 3, Uncertainty management, is comprised of 3 subthemes that describe how participants manage their uncertainty: Subtheme 1: Reassurance that breast cancer risk conferred by pathogenic variants in ATM and CHEK2 is lower than the risk conferred by those in BRCA1/2, Subtheme 2: Optimism that more data will become available over time, and Subtheme 3: Reliance on healthcare providers to share new information as it arises.

Theme 1: motivations to pursue genetic testing

Participants reported a variety of reasons as to why they sought out genetic testing for cancer susceptibility. Some chose to pursue testing after a family member tested positive for a pathogenic variant in the ATM and/or CHEK2 gene. Most suggested that motivations to seek out genetic testing arose from their positive family histories and personal experiences with family members affected with cancer. Most also stated that it was an easy decision to undergo genetic testing because of the perceived potential for test results to provide a more accurate idea of their own risk to develop cancer and the tools for early cancer detection and prevention. This highlights the idea that participants’ motivations to undergo genetic testing relate to their expectation that the results will resolve uncertainties in these areas.

It was very easy for me to make the decision [to get genetic testing]. I would rather have as much information as possible to make precautionary doctors appointments, testings, screenings in the future so I can try to catch [cancer] early… (33yo F, ATM+ and CHEK2+)

Theme 2: expressions of uncertainty

Uncertainty was apparent in participants’ descriptions of their initial reactions to receiving their genetic test results and how they perceived information about their results at the time of the study. Six major subthemes characterize these expressions of uncertainty. Among them includes participants receiving a result in an unfamiliar gene. The other five subthemes map to the three major dimensions of Han’s taxonomy (Table 3).

Theme 2, subtheme 1: receiving a result in an unfamiliar gene

Participants reported that genetic test results were initially disclosed by a genetic counselor or a nurse practitioner via telephone or through an in-person visit. Most participants met with a genetic counselor to discuss their test results. A majority of participants recalled feeling unfamiliar with ATM/CHEK2 when they first received their results.

I saw that I have this positive for, I don’t know, I don’t even know how to say this word. Ataxia something? (38yo F, ATM+)

This unfamiliarity reflects the initial uncertainties participants experienced upon receiving their results. In some cases, this led to a perceived lack of clarity around the implications a positive test result had for their health.

What’s [this test result] going to do to change your life on a day-to-day basis? (51yo M, ATM +)

What does that [CHEK2] mean? I have something? I’m dying? What’s up? (46yo F, CHEK2 +)

Theme 2, subtheme 2: probability of developing cancer (source of uncertainty)

Participants highlighted the probability and timing of developing cancer as a source, or cause, of uncertainty:

I’m going to have cancer now? Or I have cancer now? Is [it] going to be in the first year, when? When [is] this going to appear? I didn’t know nothing about the topic. What does it mean? It’s sure that I'm going to have cancer? That means, that one day in my life I am going to have cancer? (46yo F, CHEK2+)

Additionally, participants who tested positive for both an ATM and a CHEK2 pathogenic variant voiced uncertainty regarding the probability of developing cancer in the context of having two pathogenic variants in different genes.

After I got the information [genetic test results], again I had to do a little bit more research as far as what’s going on, but I was not clear, because whenever I was reading, it said that anybody who has this type of a genetic mutation, the chances are 50%, and then the other one the chances are 70%. When you add these up, it gives you such a huge number that you think that you already have cancer and you don’t know it. (58yo F, ATM+ and CHEK2+)

Risk estimates for participants who harbored pathogenic variants in both genes were clarified after meeting with a genetic counselor. One participant summarized their genetic counselor as saying to them that: “having two genes does not multiply my risks, or double it” (32yo F, ATM + and CHEK2 +).

Theme 2, subtheme 3: ambiguous cancer risk data (source of uncertainty)

Participants often described that the data around the magnitude of cancer risk and types of cancer that are potentially associated with their variant is not yet well-established. This indicates that participants viewed this data as ambiguous, meaning they perceive the available information about their variant as “unavailable, inadequate, or imprecise” [23], giving rise to uncertainty.

I’m trying to remember even what the specifics [were] ... I think breast was the one that they highlighted the most, but I think ovarian was brought up. And then I think the others, it’s really hazy data, I think. I think they just don’t have maybe enough to have a really strong correlation. (28yo F, ATM+)

Theme 2, subtheme 4:ambiguous data regarding the effectiveness of cancer risk management strategies (source of uncertainty)

Participants described that there is a lack of evidence around the effectiveness of certain cancer screening modalities (e.g. for pancreatic cancer) and certain cancer risk-reducing measures (e.g. chemoprevention (Tamoxifen)) that may be prescribed to patients with pathogenic ATM and/or CHEK2 variants.

They don’t have... any studies that say, oh if you take it [Tamoxifen] your risk for the CHEK2... goes down say 10%. But if you don’t take it then it’s the same risk that it was without it. So I think that would be one of the things that I would want to know. (63yo F, CHEK2+)

Participants further underscored the scarcity of information regarding cancer risk management strategies for ATM and CHEK2 by comparing this information to data available for genes with more established management guidelines, notably BRCA1/2. This comparison was made after participants were probed to provide their thoughts on the idea that more is known about BRCA1/2 than ATM and CHEK2, but some participants also offered their thoughts independent of the interview question.

I just, I wish there was more research on ATM so like I can know, like for example, my girlfriend got tested positive for the BRCA gene...So she went and did everything she needed to do and... they know the exact steps of what you need to do for that… I just wish that I was in the same position with this...ATM gene... you know, what are the steps that I need to follow other than, well, you should probably do X, Y, and Z. But that’s what I wish. I wish that there was more info. (33yo F, ATM+)

Theme 2, subtheme 5: ambiguity influences decisions about uptake of cancer risk management strategies (issue of uncertainty)

Participants’ perceptions of ambiguous data regarding the effectiveness of cancer risk management strategies influenced their decisions to engage in certain screening protocols (i.e. for pancreatic cancer) and risk-reducing measures, specifically Tamoxifen to reduce risk of breast cancer. Particularly, participants described being less likely to engage in these protocols because they perceive there is inadequate effectiveness information about them.

But until there’s more info there, I don’t think I need to be putting this medication [Tamoxifen] in my body to make me feel the way I did. (33yo F, ATM+)

Theme 2, subtheme 6: clinician uncertainty towards management recommendations (locus of uncertainty)

Finally, participants illustrated various loci of uncertainty they encountered as they navigated the implications of their genetic test results. Participants described uncertainty among health care providers such as genetic counselors, internists and oncologists.

A lot of people haven't heard of it [CHEK2]. Even the genetic counselor said they just don't have that much information on it. (46yo F, CHEK2+)

This highlights that uncertainties are not only experienced by participants, but also among those they interact with. Furthermore, the presence of various loci was also depicted as an issue of uncertainty as shared uncertainty among participants and their clinicians was described to influence participants’ decisions around whether or not to engage in cancer risk management strategies.

And then the doctor recommended or suggested I take one or two drugs to inhibit potential breast cancer, but it wasn't like: ‘you should take it’. It was just like: ‘we have this, you could take this’. And so that wasn’t helpful. I mean it was and it wasn’t helpful. Oh, there’s something there, but oh, should I take it? I don't know. (65yo F, ATM+)

Theme 3: uncertainty management

In addition to expressing specific areas of uncertainty, participants described three ways they deal with the uncertainties that arose from their genetic test results: reassurance that breast cancer risk conferred by pathogenic variants in ATM and CHEK2 is lower than the risk conferred by those in BRCA1/2, optimism that more data will become available over time, and reliance on healthcare providers to share new information as it arises.

Theme 3, subtheme 1: reassurance that breast cancer risk conferred by pathogenic variants in ATM and CHEK2 is lower than the risk conferred by those in BRCA1/2

Despite learning they are of a heightened predisposition to develop cancer, participants reported relief in their relatively lower risk to develop cancer compared to individuals who harbor pathogenic variants in high-risk genes, such as BRCA1/2.

Yeah, I guess I was kind of relieved. I mean, it wasn't the best news that we had that in general, the CHEK2, but I was relieved that it wasn’t the BRCA because I knew that one was really bad. (35yo F, CHEK2+)

Theme 3, subtheme 2: optimism that more data will become available over time

Participants suggested their level of confidence in cancer risk management strategies depends on the strength of data available for them.

Also, whatever evidence could be provided for a treatment plan or screening plan, the more evidence and knowledge, the more reassured I’ll feel that it’s ... good… (28yo F, ATM+)

Participants also described their expectations that this data would become increasingly more available. They often spoke to their belief in the potential for scientific advances within the cancer genetics field.

I mean, we probably didn’t know much of any of this, how many years ago? We’re just kind of ... I don’t want to say scratching the surface, but just finding so much more out and more out and more out… (33yo F, ATM+ and CHEK2+)

One participant described the potential for certainty from future data by comparing possible breakthroughs for CHEK2 to those accomplished with BRCA1/2.

I mean, I’m pretty sure that eventually it’s going to become more well-known like the BRCA gene, because technology is just working overtime nowadays. People are finding out way more things, and testing, and all that. Eventually it will probably get as much research and answers as the BRCA gene. (35yo F, CHEK2+)

Theme 3, subtheme 3: reliance on healthcare providers to share new information as it arises

Participants expected genetic counselors and other healthcare providers involved in their cancer risk management to keep them updated with new information about ATM and/or CHEK2. Specifically, if and when new data regarding these genes arises that may influence current recommendations for cancer risk-reducing interventions and surveillance tools. This suggests that participants believe they can (and should) depend on their clinicians to manage their health appropriately, and use this reliance as a way to manage the perceived uncertainty they have about their genetic test result.

I’ve only researched [my gene/variant] a couple years ago, so I would have the anticipation that my GP [general practitioner/primary care provider] and everybody else in my care would alert me to something new, because I’m not reading it every day. (54yo F, CHEK2+)

I mean hopefully my gynecologist is on top of things because she’s the one that’s scheduling everything for me. Hopefully the hospitals I’m going to and the tests [I’m] taking, they are skilled at what they do. I mean I have no idea. I’m not a doctor so I just have to rely on the medical community to do what they do. (46yo F, CHEK2+)

Discussion and conclusion

Discussion

Our study sought to explore and characterize the uncertainty experienced by carriers of pathogenic variants in the moderate-risk cancer genes ATM and CHEK2, drawing on Han’s taxonomy of uncertainty. Consistent with other literature [33,34,35], our study found that participants undergo genetic testing because they expect that genetic test results will provide clarification regarding their cancer risks and clear recommendations on how to manage these risks. However, current scientific knowledge for genes such as ATM and CHEK2 may not actually lead to such clarification or recommendations. Consequently, despite being identified as a carrier of a pathogenic variant in a (moderate-risk) cancer risk gene, our participants continued to experience ongoing uncertainties about cancer risk and management after receiving their genetic test results. In addition, there was a sense that participants had not anticipated this as they had not considered that a pathogenic finding would still leave uncertainty. These uncertainties mapped to the dimensions of uncertainty delineated by Han and colleagues [23]. Importantly, these uncertainties impacted the subsequent approaches that participants took to their screening and management for cancer risk. Participants additionally looked to healthcare providers to manage this for them, especially as new information arises in the future.

Source was the most often reported dimension of uncertainty among participants, with the most prominent being related to ambiguity of available prognostic data around ATM and CHEK2. Ambiguity is a commonly cited source of uncertainty among studies that have used Han’s taxonomy in their investigations of patient-expressed uncertainty [36, 37]. Specifically in our study, ambiguity was highlighted in participant descriptions of current cancer risk data for ATM and CHEK2. Interestingly, participants with pathogenic variants in both ATM and CHEK2 described uncertainty around whether carrying pathogenic variants in both genes compounds their cancer risks, revealing a unique source of uncertainty specific to undergoing multigene panel testing. Participants also described the data around the effectiveness of current risk management options for breast and other associated cancer types for these two genes as ambiguous. This aligns with Esteban and colleagues’ hypothesis that high levels of uncertainty observed in moderate-risk variant carriers is due to the lack of robust risk estimates for certain cancers and the effectiveness of management and surveillance options available for them [13].

An issue of uncertainty occurred related to participants’ perceptions of ambiguous data regarding the effectiveness of cancer risk management strategies available for ATM and CHEK2 and their internal conflict over whether to engage with certain cancer risk management strategies and early cancer detection tools. Specifically, our findings demonstrated that participants’ perception of a lack of robust data around the use of Tamoxifen and limited effectiveness data of pancreatic cancer screening for carriers of pathogenic ATM and/or CHEK2 variants influenced their decisions to engage in these management approaches, with some participants ultimately choosing not to. The decision to forgo certain management options may reflect “ambiguity aversion”, where individuals avoid medical treatment or tests because of incomplete or conflicting information about said treatment or tests [38]. Aversion to ambiguous data has been previously shown to be associated with decreased participation in cancer risk management strategies. For instance, in a study of women identified to have dense breast tissue, and are thus at increased risk to develop breast cancer, women who achieved higher scores on an ambiguity aversion measure demonstrated lower intentions to participate in mammography and ultrasound screening [39]. This may be attributed to the conflicting information over how effective mammography and ultrasound is for women with dense breast tissue. It is possible that our participants may have been less likely to participate in cancer risk management strategies currently available for carriers of pathogenic ATM/CHEK2 variants due to ambiguity aversion. However, our study did not specifically assess participants’ tolerance for ambiguity or whether this specifically impacted their decisions to participate in cancer risk management strategies. Future research should look into if and how ambiguity aversion may affect moderate-risk variant carriers’ willingness to participate in such management strategies.

Furthermore, acknowledgement of uncertainty regarding the aforementioned cancer risk management strategies among various loci, including clinicians, was shown to influence participants’ decisions to engage in such strategies. Our finding related to locus of uncertainty suggests that clinicians’ expressions of uncertainty regarding certain cancer risk management approaches may influence moderate-risk variant carriers’ decisions related to whether or not to partake in them. Other reports have demonstrated an association between clinicians providing education on the uncertainties for controversial cancer screening procedures and influence on patient interest in those procedures [40, 41]. One study surveying physician attitudes towards discussing medical interventions associated with uncertainty with patients showed that physicians would be more likely to withhold such interventions if they perceive their patients will have negative reactions to ambiguous information [42]. As clinicians have a vital role in imparting information about various tests and procedures, especially those that are marked with uncertainty, it is imperative that they are able to accurately assess and understand their patients uncertainty in order to assist them in adapting to the implications of such uncertainty.

Despite the relative unknowns our participants perceived regarding their cancer risks, they seemed to find some sense of relief from uncertainty in their perception that the cancer risk conferred by ATM and CHEK2 is relatively lower than the risk conferred by BRCA1/2. In a study conducted by Scherr and colleagues, participants experienced relief when they interpreted their ambiguous genetic test results to mean they did not have to consider invasive procedures, such as a prophylactic double mastectomy, which is often a consideration for individuals with pathogenic BRCA1/2 variants and can be associated with negative effects on body image, sexuality, and satisfaction with intimacy [43, 44]. Perhaps our participants’ relief stemmed from a similar interpretation of their results as they perceive their cancer risk to be lower than individuals with pathogenic BRCA1/2 variants, and so they can avoid making difficult decisions about undergoing such invasive and potentially life-altering procedures.

Comparisons of ATM and CHEK2 to BRCA1/2 was common among our participants, in both descriptions of the amount of cancer risk and risk management data available for these genes. It should be noted that participants were asked to provide their thoughts on the idea that more is known about BRCA1/2 than ATM and CHEK2, but some participants also offered their thoughts independent of the interview question(s) on this topic. Portrayal of BRCA1/2 as the “gold standard” to which genes with less robust data can be compared has been documented in discussions of risk communication between clinicians and patients within the cancer genetics setting [45]. Our finding suggests the possibility that our participants use data for BRCA1/2 as a point of reference, or “anchor”, as a way to compare magnitude of cancer risks and potential risk management strategies for their specific variant. Although our participants may find reassurance in their relatively lower risk to develop cancer compared to carriers of pathogenic variants in BRCA1/2, studies have shown that use of the anchor heuristic does not allow for sufficient adjustment of one’s subjective risk to their objective risk [46]. This may have implications for patients’ informed decision making regarding cancer risk management in the case that pathogenic variants within moderate-risk genes confer a higher or lower cancer risk than is currently reported and patients have already anchored themselves to their own subjective risk to develop cancer.

We found that participants in our study were reassured by the idea that future developments in the cancer genetics field aim to provide insight on how to better manage cancer risks for carriers of pathogenic ATM/CHEK2 variants. The hope for future science and technology to lead to the advancement needed to enhance one’s health is an uncertainty management strategy termed introducing uncertainty related to science by Fisher and colleagues [25]. This strategy has been demonstrated in other studies as a method of reframing uncertainty more positively [47]. Although our participants were able to find reassurance through this method, patients can only benefit from future advancements within the cancer genetics setting if they are aware of when such developments occur. Our participants expressed reliance on healthcare providers to keep them updated with advancements in the field, especially in the event that it changes current medical management. This finding suggests patients expect clinicians to notify them of any changes to their cancer risk management, which is consistent with previous investigations into cancer genetics patients’ re-contact preferences [48]. There is ongoing discussion among providers to reach consensus on re-contact procedures related to new genetic discoveries [49]. Arguments in favor of provider re-contact with new genetic information include the respect for patients’ autonomy and beneficence, while arguments against include the idea that re-contact is the patient’s responsibility and that re-contact is not feasible [50, 51]. There is importance in accounting for patients’ re-contact preferences within future discussions about re-contact protocols as our results demonstrate that patients are expectant of their providers to provide them with this information. These results additionally highlight the reliance patients have on non-genetics health professionals to provide more information and accurate management for their variant. As the role for non-genetics health professionals to provide genetic services is increasing, so are investigations into the quality of such services [52]. These investigations should examine the potential impact non-genetics providers play in re-contacting patients regarding new genetic information.

Practice implications

In our study, the amount of uncertainty our participants encountered, specific to being unfamiliar with the ATM and/or CHEK2 gene(s), risks (most notably whether having pathogenic variants in both genes compounds cancer risk), and management add to the ongoing debate about the clinical actionability of multigene panels for cancer susceptibility. Arguments in favor of using more limited panels cite that broad multigene panel testing may invoke anxieties in individuals who undergo such testing. However, since large multigene panels continue to be widely utilized, our insight into uncertainty can help to inform how information regarding moderate-risk genes should be presented during pre- and post-test discussions in order to help individuals anticipate and address these potential anxieties.

Current genetic counseling models, such as the “tiered and binned” approach developed by Bradbury and colleagues [3], already offer suggestions on how clinicians can present information in a way that helps individuals anticipate uncertain information that can arise from broad cancer susceptibility multigene panels. Our findings may help to supplement such models as we provide insight on psychological effects of offering such testing, specifically the actual uncertainties a subset of these individuals encounter. Using Han’s taxonomy may also be helpful to further characterize the uncertainties of other individuals who undergo such testing. In the context of increasing use of multigene panels for cancer susceptibility—and thus the increasing identification of individuals found to carry pathogenic variants in ATM, CHEK2, and other genes that may have limited clinical utility data—effective education and counseling about uncertainty is crucial to helping individuals anticipate uncertain results and promote adaptation to them.

As outlined in Table 4, the authors offer recommendations around how our findings can be used to help inform clinician communication around uncertainty during pre- and post-test counseling. Given the uncertainties that arose among our participants after being identified as carriers of pathogenic ATM and/or CHEK2 variants, providers may wish to emphasize the ambiguity of cancer risk and management of data that exists for certain variants, as this was the most prominent source of uncertainty identified among our participants. Patients should be made aware that the information they receive from genetic testing may not enable clinical action due to the ambiguous data that exists for them. Clinicians may also wish to highlight the idea that ambiguous data may influence decisions around uptake of certain cancer risk management strategies, an issue of uncertainty identified in the current study. Addressing the potential anxieties that may arise as a result of perceived ambiguity around these cancer prevention strategies during pre-test counseling can aid decision-making around whether or not genetic testing in the first place is appropriate for them. Similarly, highlighting these uncertainties during post-test counseling sessions can help to inform patients’ decisions around engaging in available risk management strategies. Clinicians should also be aware of their own influence on patients’ decisions to engage in cancer risk management strategies, as well as their own reactions to how they perceive their patients will react to uncertain information, as we demonstrated how perspectives of uncertainty among various loci impacts patients’ decision-making.

Table 4 Findings relating to uncertainty and how clinicians may choose to facilitate patient adaptation to uncertainty related to multigene panel testing for cancer susceptibility

Limitations

Our study recruited participants from a single academic medical center, which is reflected in the limited sociodemographic diversity and may not align with the perspectives of other individuals who harbor pathogenic variants in the ATM and/or CHEK2 gene(s). Similarly, uncertainties perceived by our participants may only be inherent to the cancer genetics clinic they were recruited from as other institutions may have different practices on addressing uncertainties. Participants who answered the demographic survey and participated in interviews may reflect a biased sample of individuals who were interested in answering questions about their genetic testing experience and understanding of their test results. These individuals may have also been inherently more uncertain about their results and sought out participation in our study in hopes of gaining clarification. However, bias does not apply as a valid critique of qualitative research as participants’ subjectivity is crucial to understanding their experiences, perspectives and values [53]. Perspectives were also limited in that a majority of participants were female, although the gender identity of the interviewees (80% female) was proportionate to that of the population who met the inclusion criteria (79% female). A majority of female participants may also be attributed to the classification of ATM/CHEK2 as “moderate-risk breast cancer genes” within the context of breast cancer being much more commonly diagnosed in females than in males, as well as the lack of genetic information and resources directed towards males [54]. Again, it should be noted that participants were unaffected by cancer, and so it is possible that carriers of moderate-risk variants affected by cancer may encounter different uncertainties. We did not account for whether there may be differences in perceived uncertainties among our participants depending on the amount of time elapsed since they received their genetic test results. Thus, we cannot assess whether perceptions of uncertainty have changed or will change.

Conclusion

We highlight areas of source, issue, and loci of uncertainty expressed by carriers of pathogenic ATM and/or CHEK2 variants. Having clinicians (overtly) address these areas of uncertainty during pre- and post-test counseling sessions may further promote patient adaptation to multigene panel testing for cancer susceptibility, especially in contexts where panels include genes with evolving cancer risk and management data. Standardizing re-contact guidelines among cancer genetics clinicians may also help patients understand what to expect as new knowledge arises. Research is needed to assess the feasibility of proposed suggestions to uncertainty communication as well as how recipients of this communication would benefit from such changes. Use of Han’s taxonomy for other populations of carriers of pathogenic gene variants may also be useful in characterizing other uncertainties and further developing ways to meet broader needs.

Data availability

Upon request, the raw data supporting the conclusions of this article will be made available by the authors.

Code availability

Coding of interview transcripts was facilitated by Dedoose (Version 8.2.14, 2019).

References

  1. 1.

    Idos GE, Kurian AW, Ricker C et al (2019) Multicenter prospective cohort study of the diagnostic yield and patient experience of multiplex gene panel testing for hereditary cancer risk. JCO Precis Oncol 3:1–19. https://doi.org/10.1200/PO.18.00217

    Article  Google Scholar 

  2. 2.

    Rainville IR, Rana HQ (2014) Next-generation sequencing for inherited breast cancer risk: counseling through the complexity. Curr Oncol Rep 16:371. https://doi.org/10.1007/s11912-013-0371-z

    CAS  Article  PubMed  Google Scholar 

  3. 3.

    Bradbury AR, Patrick-Miller L, Long J et al (2015) Development of a tiered and binned genetic counseling model for informed consent in the era of multiplex testing for cancer susceptibility. Genet Med 17:485–492. https://doi.org/10.1038/gim.2014.134

    Article  PubMed  Google Scholar 

  4. 4.

    Cybulski C, Wokołorczyk D, Jakubowska A et al (2011) Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29:3747–3752. https://doi.org/10.1200/JCO.2010.34.0778

    CAS  Article  PubMed  Google Scholar 

  5. 5.

    Mavaddat N, Peock S, Frost D et al (2013) Cancer risks for BRCA1 and BRCA2 mutation carriers: results from prospective analysis of EMBRACE. JNCI J Natl Cancer Inst 105:812–822. https://doi.org/10.1093/jnci/djt095

    CAS  Article  PubMed  Google Scholar 

  6. 6.

    Marabelli M, Cheng S-C, Parmigiani G (2016) Penetrance of ATM gene mutations in breast cancer: a meta-analysis of different measures of risk. Genet Epidemiol 40:425–431. https://doi.org/10.1002/gepi.21971

    Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Catana A, Apostu AP, Antemie R-G (2019) Multi gene panel testing for hereditary breast cancer - is it ready to be used? Med Pharm Rep 92:220–225. https://doi.org/10.15386/mpr-1083

    Article  PubMed  PubMed Central  Google Scholar 

  8. 8.

    Cella D, Hughes C, Peterman A et al (2002) A brief assessment of concerns associated with genetic testing for cancer: the multidimensional impact of cancer risk assessment (MICRA) questionnaire. Health Psychol 21:564–572. https://doi.org/10.1037/0278-6133.21.6.564

    Article  PubMed  Google Scholar 

  9. 9.

    Hall MJ, Patrick-Miller LJ, Egleston BL et al (2018) Use and patient-reported outcomes of clinical multigene panel testing for cancer susceptibility in the multicenter communication of genetic test results by telephone study. JCO Precis Oncol 2:1–12. https://doi.org/10.1200/po.18.00199

    Article  Google Scholar 

  10. 10.

    Di Prospero LS, Seminsky M, Honeyford J et al (2001) Psychosocial issues following a positive result of genetic testing for BRCA1 and BRCA2 mutations: findings from a focus group and a needs-assessment survey. CMAJ Can Med Assoc J 164:1005–1009

    Google Scholar 

  11. 11.

    Claes E, Evers-Kiebooms G, Denayer L et al (2005) Predictive genetic testing for hereditary breast and ovarian cancer: psychological distress and illness representations 1 year following disclosure. J Genet Couns 14:349–363. https://doi.org/10.1007/s10897-005-1371-4

    CAS  Article  PubMed  Google Scholar 

  12. 12.

    Oliveri S, Ferrari F, Manfrinati A, Pravettoni G (2018) A systematic review of the psychological implications of genetic testing: a comparative analysis among cardiovascular, neurodegenerative and cancer diseases. Front Genet 9:624. https://doi.org/10.3389/fgene.2018.00624

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Esteban I, Vilaró M, Adrover E et al (2018) Psychological impact of multigene cancer panel testing in patients with a clinical suspicion of hereditary cancer across Spain. Psycho Oncol 27:1530–1537. https://doi.org/10.1002/pon.4686

    CAS  Article  Google Scholar 

  14. 14.

    Tung N, Domchek SM, Stadler Z et al (2016) Counselling framework for moderate-penetrance cancer-susceptibility mutations HHS Public Access. Nat Rev Clin Oncol 13:581–588. https://doi.org/10.1038/nrclinonc.2016.90

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. 15.

    National Comprehensive Cancer Network (NCCN) (2020) Genetic/familial high-risk assessment: breast, ovarian, and pancreatic (version 1.2021). https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf. Accessed 15 Sep 2020

  16. 16.

    Kurian AW, Antoniou AC, Domchek SM (2016) Refining breast cancer risk stratification: additional genes, additional information. Am Soc Clin Oncol Educ Book 36:44–56. https://doi.org/10.1200/EDBK_158817

    Article  Google Scholar 

  17. 17.

    West AH, Blazer KR, Stoll J et al (2018) Clinical interpretation of pathogenic ATM and CHEK2 variants on multigene panel tests: navigating moderate risk. Fam Cancer 17:495–505. https://doi.org/10.1007/s10689-018-0070-x

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Kurian AW, Hughes E, Handorf EA et al (2017) Breast and ovarian cancer penetrance estimates derived from germline multiple-gene sequencing results in women. JCO Precis Oncol 1:1–12. https://doi.org/10.1200/PO.16.00066

    Article  Google Scholar 

  19. 19.

    Pilié PG, Johnson AM, Hanson K et al (2017) Germline genetic variants in men with prostate cancer and one or more additional cancers. Cancer 123:3925–3932. https://doi.org/10.1002/cncr.30817

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Shindo K, Yu J, Suenaga M et al (2017) Deleterious germline mutations in patients with apparently sporadic pancreatic adenocarcinoma. J Clin Oncol 35:3382–3390. https://doi.org/10.1200/JCO.2017.72.3502

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    National Comprehensive Cancer Network (2020) Genetic/familial high-risk assessment: colorectal (Version 1.2020). https://www.nccn.org/professionals/physician_gls/pdf/genetics_colon.pdf. Accessed 15 Sep 2020

  22. 22.

    Bartley N, Napier C, Best M, Butow P (2020) Patient experience of uncertainty in cancer genomics: a systematic review. Genet Med 22:1450–1460. https://doi.org/10.1038/s41436-020-0829-y

    Article  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Han PKJ, Umstead KL, Bernhardt BA et al (2017) A taxonomy of medical uncertainties in clinical genome sequencing. Genet Med 19:918–925. https://doi.org/10.1038/gim.2016.212

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Dean M (2016) “It’s not if I get cancer, it’s when I get cancer”: BRCA-positive patients’ (un)certain health experiences regarding hereditary breast and ovarian cancer risk. Soc Sci Med 163:21–27. https://doi.org/10.1016/j.socscimed.2016.06.039

    Article  PubMed  Google Scholar 

  25. 25.

    Fisher CL, Roccotagliata T, Rising CJ et al (2017) “I don’t want to be an Ostrich”: managing mothers’ uncertainty during BRCA1/2 genetic counseling. J Genet Couns 26:455–468. https://doi.org/10.1007/s10897-016-9998-x

    Article  PubMed  Google Scholar 

  26. 26.

    Rauscher EA, Dean M, Campbell-Salome GM (2018) “I am uncertain about what my uncertainty even is”: men’s uncertainty and information management of their BRCA-related cancer risks. J Genet Couns 27:1417–1427. https://doi.org/10.1007/s10897-018-0276-y

    Article  PubMed  Google Scholar 

  27. 27.

    Vaismoradi M, Turunen H, Bondas T (2013) Content analysis and thematic analysis: implications for conducting a qualitative descriptive study. Nurs Health Sci 15:398–405. https://doi.org/10.1111/nhs.12048

    Article  PubMed  Google Scholar 

  28. 28.

    Saunders B, Sim J, Kingstone T et al (2018) Saturation in qualitative research: exploring its conceptualization and operationalization. Qual Quant 52:1893–1907. https://doi.org/10.1007/s11135-017-0574-8

    Article  PubMed  Google Scholar 

  29. 29.

    DeCuir-Gunby JT, Marshall PL, McCulloch AW (2011) Developing and using a codebook for the analysis of interview data: an example from a professional development research project. Field Methods 23:136–155. https://doi.org/10.1177/1525822X10388468

    Article  Google Scholar 

  30. 30.

    Barbour RS (2001) Education and debate Checklists for improving rigour in qualitative research: a case of the tail wagging the dog? BMJ 322:1115. https://doi.org/10.1136/bmj.322.7294.1115

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Guest G, MacQueen KM (2008) Handbook for team-based qualitative research. Rowman Altamira

  32. 32.

    Campbell JL, Quincy C, Osserman J, Pedersen OK (2013) Coding in-depth semistructured interviews: problems of unitization and intercoder reliability and agreement. Sociol Methods Res 42:294–320. https://doi.org/10.1177/0049124113500475

    Article  Google Scholar 

  33. 33.

    Hughes C, Gomez-Caminero A, Benkendorf J et al (1997) Ethnic differences in knowledge and attitudes about BRCA1 testing in women at increased risk. Patient Educ Couns 32:51–62. https://doi.org/10.1016/S0738-3991(97)00064-5

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    Kessler L, Collier A, Brewster K et al (2005) Attitudes about genetic testing and genetic testing intentions in African American women at increased risk for hereditary breast cancer. Genet Med 7:230–238. https://doi.org/10.1097/01.GIM.0000159901.98315.FE

    Article  PubMed  Google Scholar 

  35. 35.

    Scott D, Friedman S, Telli ML, Kurian AW (2020) Decision making about genetic testing among women with a personal and family history of breast cancer. JCO Oncol Pract 16:e37–e55. https://doi.org/10.1200/JOP.19.00221

    Article  PubMed  Google Scholar 

  36. 36.

    Makhnoon S, Shirts BH, Bowen DJ (2019) Patients’ perspectives of variants of uncertain significance and strategies for uncertainty management. J Genet Couns 28:313–325. https://doi.org/10.1002/jgc4.1075

    Article  PubMed  Google Scholar 

  37. 37.

    Medendorp NM, Hillen MA, Murugesu L et al (2019) Uncertainty related to multigene panel testing for cancer: a qualitative study on counsellors’ and counselees’ views. J Commun Genet 10:303–312. https://doi.org/10.1007/s12687-018-0393-1

    Article  Google Scholar 

  38. 38.

    Han PKJ, Reeve BB, Moser RP, Klein WMP (2009) Aversion to ambiguity regarding medical tests and treatments: measurement, prevalence, and relationship to sociodemographic factors. J Health Commun 14:556–572. https://doi.org/10.1080/10810730903089630

    Article  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Yeh VM, Schnur JB, Margolies L, Montgomery GH (2015) Dense breast tissue notification: impact on women’s perceived risk, anxiety, and intentions for future breast cancer screening. J Am Coll Radiol JACR 12:261–266. https://doi.org/10.1016/j.jacr.2014.11.001

    Article  PubMed  Google Scholar 

  40. 40.

    Jepson RG, Forbes CA, Sowden AJ, Lewis RA (2001) Increasing informed uptake and non-uptake of screening: evidence from a systematic review. Health Expect Int J Public Particip Health Care Health Policy 4:116–130. https://doi.org/10.1046/j.1369-6513.2001.00143.x

    CAS  Article  Google Scholar 

  41. 41.

    Volk RJ (2003) Patient education for informed decision making about prostate cancer screening: a randomized controlled trial with 1-year follow-up. Ann Fam Med 1:22–28. https://doi.org/10.1370/afm.7

    Article  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Portnoy DB, Han PKJ, Ferrer RA et al (2013) Physicians’ attitudes about communicating and managing scientific uncertainty differ by perceived ambiguity aversion of their patients. Health Expect 16:362–372. https://doi.org/10.1111/j.1369-7625.2011.00717.x

    Article  PubMed  Google Scholar 

  43. 43.

    Glassey R, O’Connor M, Ives A et al (2018) Heightened perception of breast cancer risk in young women at risk of familial breast cancer. Fam Cancer 17:15–22. https://doi.org/10.1007/s10689-017-0001-2

    Article  PubMed  Google Scholar 

  44. 44.

    Scherr CL, Ramesh S, Getachew-Smith H et al (2020) How patients deal with an ambiguous medical test: decision-making after genetic testing. Patient Educ Couns. S0738-3991(20)30557-7. https://doi.org/10.1016/j.pec.2020.10.020

  45. 45.

    Waltz M, Prince AER, O’Daniel JM et al (2020) Referencing BRCA in hereditary cancer risk discussions: In search of an anchor in a sea of uncertainty. J Genet Couns 4:1219. https://doi.org/10.1002/jgc4.1219

    Article  Google Scholar 

  46. 46.

    Senay I, Kaphingst KA (2009) Anchoring-and-adjustment bias in communication of disease risk. Med Decis Making 29:193–201. https://doi.org/10.1177/0272989X08327395

    Article  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Solomon I, Harrington E, Hooker G et al (2017) Lynch syndrome limbo: patient understanding of variants of uncertain significance. J Genet Couns 26:866–877. https://doi.org/10.1007/s10897-017-0066-y

    Article  PubMed  Google Scholar 

  48. 48.

    Griffin CA, Axilbund JE, Codori AM et al (2007) Patient preferences regarding recontact by cancer genetics clinicians. Fam Cancer 6:265–273. https://doi.org/10.1007/s10689-007-9117-0

    Article  PubMed  Google Scholar 

  49. 49.

    David KL, Brenman LM, Bush L et al (2019) Patient re-contact after revision of genomic test results: points to consider—a statement of the American College of Medical Genetics and Genomics (ACMG). Genet Med 21:769–771. https://doi.org/10.1038/s41436-018-0391-z

    Article  PubMed  Google Scholar 

  50. 50.

    Otten E, Plantinga M, Birnie E et al (2015) Is there a duty to recontact in light of new genetic technologies? A systematic review of the literature. Genet Med 17:668–678. https://doi.org/10.1038/gim.2014.173

    CAS  Article  PubMed  Google Scholar 

  51. 51.

    Giesbertz NAA, van Harten WH, Bredenoord AL (2019) A duty to recontact in genetics: context matters. Nat Rev Genet 20:371–372. https://doi.org/10.1038/s41576-019-0121-7

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Bensend TA, Veach PM, Niendorf KB (2014) What’s the harm? Genetic counselor perceptions of adverse effects of genetics service provision by non-genetics professionals. J Genet Couns 23:48–63. https://doi.org/10.1007/s10897-013-9605-3

    Article  PubMed  Google Scholar 

  53. 53.

    Braun V, Clarke V (2013) Successful qualitative research: a practical guide for beginners. SAGE

  54. 54.

    Dean M, Campbell-Salome G, Rauscher EA (2020) Engaging men with brca-related cancer risks: practical advice for BRCA risk management from male stakeholders. Am J Mens Health 14:1557988320924932. https://doi.org/10.1177/1557988320924932

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was completed in partial fulfillment of the requirements of the first author’s Master of Science degree in Human Genetics and Genetic Counseling from Stanford University’s School of Medicine. This work has been supported by the Jane Engelberg Memorial Fellowship Student Research Award, provided by the Engelberg Foundation to the National Society of Genetic Counselors, Inc. We wish to thank the participants of this study for providing their time and their thoughtful responses, and Janine Bruce and Sylvia Bereknyei Merrell for their qualitative methods guidance throughout the study.

Funding

This work was supported by the Jane Engelberg Memorial Fellowship Student Research Award, provided by the Engelberg Foundation to the National Society of Genetic Counselors, Inc.

Author information

Affiliations

Authors

Contributions

Authors KGR, MG, AJN, and KEO designed and conceptualized the study and created the interview guide. KGR conducted all interviews. Development of the codebook and the analysis process was performed primarily by KGR and CC, with assistance from MG and KEO. All authors interpreted these results and developed themes. The first draft of the manuscript was written by KGR, and all authors provided critical feedback and approval of several drafts and the final manuscript.

Corresponding author

Correspondence to Kelly E. Ormond.

Ethics declarations

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Stanford University Institutional Review Board (09/18/2019; #51975).

Consent to participate

A waiver of written documentation of informed consent was granted, given the minimal risk of the study. Participants reviewed an information sheet prior to completing the demographic survey and provided verbal consent at the start of the interview.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 195 kb)

Supplementary file2 (XLSX 11 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Reyes, K.G., Clark, C., Gerhart, M. et al. “I wish that there was more info”: characterizing the uncertainty experienced by carriers of pathogenic ATM and/or CHEK2 variants. Familial Cancer (2021). https://doi.org/10.1007/s10689-021-00251-3

Download citation

Keywords

  • Uncertainty
  • ATM
  • CHEK2
  • Cancer genetics
  • Genetic testing
  • Qualitative research