Patient-Reported Outcomes following Genetic Testing for Familial Hypercholesterolemia, Breast and Ovarian Cancer Syndrome, and Lynch Syndrome: A Systematic Review

Background: Patient-reported outcomes (PROs) and PRO measures (PROMs) are real-world evidence that can help capture patient experiences and perspectives regarding a clinical intervention such as genetic testing. Objective: To identify and capture methods and qualitative PRO themes among studies reporting PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Methods: A systematic review was conducted via PubMed/MEDLINE, EMBASE, and Yale University’s TRIP Medical Databases on articles published by April 2021. Results: We identified 24 studies published between 1996 and 2021 representing 4279 participants that reported PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome. Studies collected and reported PROs from validated PROM instruments (n = 12; 50%), validated surveys (n = 7; 26%), and interviews (n = 10; 42%). PRO themes ranged across all collection methods (e.g., psychological, knowledge, coping and satisfaction, concern about stigma/discrimination, etc.). Conclusions: Important gaps identified include (1) most studies (n = 18; 75%) reported PROs following genetic testing for breast and ovarian cancer, and (2) populations reporting PROs overall were largely of White/Caucasian/Northern European/Anglo-Saxon descent. We offer recommendations and describe real-world implications for the field moving forward.


Introduction
Patient-reported outcomes (PROs) are surrogate endpoints that can help clinicians and researchers understand and document the patient journey [1]. PROs most notably capture data about personal utility from the patient perspective and includes patient preferences, complaints, and/or opinions before and following an intervention. When used in conjunction with more novel forms of person-generated health data, PROs offer valuable insights into the daily experiences of managing disease burden and real-world effectiveness and utility of interventions from the patient point of view [2,3].
For instance, PROs provide insights into humanistic (e.g., emotional status) and economic (e.g., out-of-pocket costs) outcomes following an intervention, which typically include anxiety or depression levels, functional status, and overall experience and satisfaction [4]. PROs are, therefore, valuable because they provide insights into what or how patients feel as well as how they value clinical interventions [2].
Generally, five broad categories of PROs have been described in the literature and can be quantitatively assessed as PRO measures (PROMs) using surveys: health-related quality of life, functional status, symptoms and symptom burden, health behaviors, and the patient's health care experience [5]. Each PRO category is accompanied by its own strengths and limitations when PROs are collected and processed in a structured form as PROMs (see Table 1, adopted by Cella et al., as examples of PROs) [5]. Table 1. Main characteristics of patient-reported outcomes (PROs outlined by Cella et al.) [5].

PRO Category Main Characteristics Main Strengths Main Limitations
Health-related quality of life (HRQL) -Is multidimensional -Can be generic or condition-specific

Background and Purpose
PROs have provided meaningful insight into individuals' and their family members' real or perceived genetic health status and offer opportunities for patients to convey their concerns, including experiences with insurance discrimination and/or access issues with insurance coverage for genetic testing and subsequent treatments [6,7]. Cella et al.'s definition of PROs in Table 1 only partially fits within the 'personal utility' concept of genetic testing that is emerging in the literature [5,6]. Notably, a systematic literature review of empirical studies conducted by Kohler et al. delineated the personal utility of genetic testing, capturing 15 distinct elements of personal utility within two domains: personal outcomes (affective, cognitive, and behavioral) and social outcomes [6]. Therefore, further exploration, crosswalk analysis, and interpretation of PROs following genetic testing are warranted for a variety of medical conditions to inform both clinical practice and policy [6,8,9].
Additionally, prior work has summarized studies on how PROs from clinical genetic testing can translate into patient empowerment [10]. In our prior work, we observed and acknowledged that PROs were underreported following genetic testing for familial hypercholesterolemia (FH) [11]. We also concluded that further investigations are needed to examine PROs following genetic testing for familial conditions falling under the United States (US) Centers for Disease Control and Prevention (CDC) Tier 1 genomic application category (FH, hereditary breast and ovarian cancer syndrome, and Lynch syndrome) [11]. Murray et al. described in their National Academy of Medicine discussion report 'Tier 1' as 'those genes with high penetrance (the probability that disease will appear when a disease-related genotype is present), well-understood links to disease, and well-established, effective interventions that result in substantial prevention or mitigation of disease or disease risk' [12]. Therefore, the purpose of this review is two-fold with regard to PROs and PROMs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome: (1) examine overarching qualitative themes among PROs and PROMs collected, measured, and reported in the literature; and (2) identify opportunities to improve existing PRO/PROM categories, collection methods, and measures to more accurately and appropriately capture and describe patient needs, perspectives, and personal utility.
To understand the larger role and impact of PROs following genetic testing for these conditions, our systematic literature review focused on the following PICO [13]: P: Patients and/or consumers with breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia.
I: Genetic testing (clinical or direct-to-consumer with a clinical intermediary) for molecular diagnosis/confirmation of breast and ovarian cancer syndrome, Lynch syndrome, and FH.
C: Patients and/or consumers with breast and ovarian cancer syndrome, Lynch syndrome, and familial hypercholesterolemia who did not undergo genetic testing.
O: PROs, personal financial/insurance coverage outcomes, humanistic outcomes (privacy, discrimination, family planning, education), and personal behavioral (treatment adherence, treatment change).

Background and Purpose
Our systematic review was divided into the following four steps in order to establish rigor in the process: (a) Database Identification and Selection, (b) Selection of Studies, (c) Data Extraction and Synthesis, and (d) Data Analysis. Preferred Reporting Items for Systematic Reviews (PRISMA) checklist items and guidelines were followed to the extent possible (www.prisma-statement.org; accessed 28 July 2020), as our review entailed a meta-synthesis of qualitative themes or data extracted from selected studies that met our inclusion criteria. Our meta-synthesis strategy draws on previous methods used by Seyedfatemi et al. in which qualitatively themes were identified and assessed in a manner that might inspire the development of a more comprehensive quantitative survey or analysis based on identified and subsequently defined themes [14].

Database Identification and Selection
Search queries for original research reports were run in PubMed/MEDLINE, EMBASE, and Yale University's TRIP Medical Database in April 2021 by one author (R.M.H-S.) using Boolean strings with both MeSH and general terms. When available, filters were used to identify human studies as well as systematic literature reviews that captured human studies focused on our PICO. Specifically, our search strategy (available from the authors on request) was adapted to each database, using terms focused on PROs and/or PROMs: PRO-related terms (e.g., anxiety, genetic testing, function, satisfaction, experience, education, psychology, privacy, knowledge, attitude, insurance coverage, healthcare expenditures/cost, cost-sharing, treatment/surveillance adherence); genetic testing (clinical or direct-to-consumer with a clinical intermediary); and breast and ovarian cancer syndrome, Lynch syndrome, and/or FH. The reference lists of relevant systematic literature reviews were also examined.

Selection of Studies
Articles published by or before April 2021 were reviewed for relevance to our stated PICO. The authors carefully selected and reviewed studies reporting PROs following genetic testing for molecular diagnosis/confirmation of breast and ovarian cancer syndrome, Lynch syndrome, and/or FH. Original research articles were excluded if they were not published in the English language and if they were case reports (n = 1). Titles and abstracts were independently screened and jointly reviewed by two authors (R.H-S. and L.J.) for relevance and the inclusion criteria (published in English; human study; original research reports focused on PROs following genetic testing for breast and ovarian cancer syndrome, Lynch syndrome, and/or FH). Studies focused on PROs following germline preimplantation genetic diagnosis and prenatal diagnosis for breast and ovarian cancer syndrome, Lynch syndrome, and/or FH were excluded. Selected papers were downloaded and merged into Zotero software (www.zotero.org; accessed 16 July 2021) for reference purposes, and duplicates were removed.

Data Extraction and Synthesis
Full-text articles that were selected for inclusion were reviewed to identify key qualitative themes regarding PROs following genetic testing for breast and ovarian cancer syndrome, Lynch syndrome, and/or FH. Attention was also paid to the geographic location of each study and whether the studies were qualitative, quantitative, or mixed-methods.
Two authors (R.H-S. and L.J.) performed data extraction using a Microsoft Excel form. One author (R.H-S.) developed and piloted this form on five studies before a second reviewer (L.J.) performed a second review to ensure completeness. A third senior author (C.Y.L.) performed a third review of the form to ensure accuracy, clarity, and relevance.
The following data were extracted from each study: Two authors (R.H-S. and L.J.) extracted the data on all studies meeting the inclusion criteria with ongoing discussion to ensure consistency, followed by a final discussion with a third senior author (C.Y.L.) to ensure accuracy and clarity regarding both descriptive information and qualitative themes extracted per article and overall.

Assessment of Methodological Quality
Although qualitative, quantitative, and mixed-methods studies were included in our analysis, we drew on previous methods used that involved the application of the Critical Appraisal Skills Programme (CASP) tool checklist for qualitative studies and trials to assess the quality of studies selected for inclusion that captured key qualitative themes along the stated PICO (www.casp-uk.net; accessed 28 July 2020) [15]. For instance, although some of the studies selected for inclusion quantitatively assessed study participant outcomes within specific qualitative domains via a survey (e.g., anxiety, depression, distress, etc.), we aimed to only capture those specific qualitative domains within each survey tool as well as the name/type of survey instruments or tools used.

Results
The search strategy identified 218 articles; titles and abstracts were screened for relevance to the stated PICO (see Figure 1). A total of 216 records were screened by title and abstract by two authors (R.H-S. and L.J.) after removing duplicates. The two authors reached an overall agreement rate of >95%. After reviewing titles and abstracts for relevance to the stated PICO, 29 papers were retrieved for full-text screening by three authors (R.H-S., C.Y.L., and L.J.). A total of 24 articles met all inclusion and exclusion criteria after full-text review. Of these, four articles that met inclusion criteria were identified and extracted from   Table 2 lists the titles, authors, and countries for each of the 24 included studies [16][17][18][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]. Table 1 also includes, for each study, the genetic disease focus or foci of each study (regarding PROs following genetic testing for breast and ovarian cancer syndrome, Lynch syndrome, and/or FH) and whether the study was qualitative, quantitative, or mixedmethods in nature. Studies were published between 1996 and 2021. Most studies were conducted in the United States (USA; n = 14), with one of these 14 studies conducted jointly between researchers within the USA and Canada. Most studies (n = 18) focused on PROs following genetic testing for breast and ovarian cancer, with one of these 18 studies focusing on breast, ovarian, and endometrial/uterine cancer. Most studies were quantitative (n = 11), followed by qualitative (n = 7), and mixed-methods studies (n = 4). Two (n = 2) studies did not explicitly report the study methods used to arrive at the qualitative themes captured.

Study and Participant Population Characteristics
There was a total of 5654 participants tested across all studies included in the review. One study (Palmquist et al., 2010) did not report the number of participants tested [35]. A total of 4279 participants across all studies provided PROs following genetic testing.
Participants were reported as genetically tested for BRCA1/2 (breast and ovarian cancer), MLH1, MSH2, MSH6, PMS2, or EPCAM (Lynch syndrome), and LDLR, APOB, or PCSK9 (FH). deWit et al. and Schneider et al. did not report specific variants tested, although the disease focus of the study was breast and ovarian cancer and Lynch syndrome, respectively [18,36]. Voorwinden et al. reported testing for BRCA1/2 for their breast and ovarian cancer participant population but did not specify variants tested for their Lynch syndrome participant population [38].  1 year, 2 years, and 3 years following testing, although the number of participants reporting PROs at 1 year (n = 796) was included in the total number of participants who provided PROs following genetic testing) [32,33]. One study collected PROs from 192 participants, with 140 participants completed qualitative interviews (Lerman et al., 1996) [27]. Two studies (Pang et al., 2018, andLee et al., 2002) did not state the number of participants reporting PROs following genetic testing [17,26]. The number of participants surveyed or interviewed across all studies ranged from 7 to 984.

PROs from Validated PROM Instruments
Several studies collected and reported PROs from validated PROM instruments (n = 12) following genetic testing (see Table 3). Of these, 11 studies reported PROs following genetic testing for breast and ovarian cancer syndrome (including breast, ovarian, and endometrial/uterine cancer). Only two studies (Esplen et al. and Voorwinden et al.) used validated PROMs to evaluate PROs following genetic testing for Lynch syndrome and none for FH genetic testing [23,38].  [18,20,21,23,28,33]. Voorwinden et al. used the Cancer Worry Scale to collect and measure participants' worries about developing cancer, the test results' influence on the participants' mood, restrictions in daily activities, and worries about cancer occurrence in or among family members [38].
Meiser et al. used the Test-Related Distress and Positive Experiences instrument to collect and measure participants' distress and positive experiences following testing [33]. Emotional Thermometers were used as an ad hoc instrument by Mella et al., who also used the Profile of Mood States instrument to capture the participants' spectrum of emotional states following testing [34]. Voorwinden et al. used the General Health Questionnaire-12 to measure and assess participants' emotional problems as an indicator of their psychological functioning [38]. Decision regret regarding surgical decision or choice and genetic testing choice was measured by Meiser et al. using the Decision Regret Scale [33].
The  [23]. Esplen also used the Demographic and Medical Information Questionnaire to assess participants' personal history of cancer, demographic factors (e.g., ethnicity, age, sex, education, occupation, age at diagnosis, if applicable, etc.), genetic test result (i.e., positive or negative), and amount of time passed since the return of their genetic test results [23].
The Ways of Coping Questionnaire and Social Support Questionnaire were used by Esplen et al. to measure the participants' coping styles (e.g., escape avoidance) and levels of social support (e.g., personal support from family and friends) following testing [23]. Esplen et al. also used the Quality of Life Index to measure the participants' family functioning following testing or return of results [23]. Lerman et al. (1996) used the Medical Outcomes Study instrument to measure participants' functional health status, specifically impairment in daily activities (i.e., role impairment) and sexual functioning following testing and return of results [27]. Although, Machanda et al. differed in that they used the Physical Health Component and Mental Health Component scale of the SF-12 instrument to measure the quality of life among participants [32].

PROs from Validated Surveys
Seven studies (n = 7) reported PROs from validated general surveys (see Table 4). The majority of these studies (n = 6) focused on breast and ovarian cancer (including breast, ovarian, and endometrial/uterine cancer). Two studies focused on Lynch syndrome, either alone or in tandem with breast and ovarian cancer. None of the studies used general surveys to evaluate PROs following FH genetic testing.

PROs from Qualitative Studies and Studies with Unreported PRO Data Collection Methods
Ten studies (n = 10) used qualitative data or other unstructured PRO data collected from study participants (see Table 5). Two studies (n = 2) reported PROs in the study discussion, but not the study results. Eight studies reported the use of qualitative interviews; one study reported the use of telephone interview assessments, and one study reported the use of focus group interviews. Two studies reported PROs but did not report data collection methods. Most of these studies (n = 8) were conducted among breast and ovarian cancer patients (including patients with endometrial/uterine cancer), although one of these studies also focused on patients with Lynch syndrome. Only two studies reported PROs following FH genetic testing. Table 5. Studies reporting qualitative data or other unstructured PRO data following genetic testing for breast and ovarian cancer syndrome, Lynch syndrome, and/or familial hypercholesterolemia (FH).

Hallowell et al. (2004) [24]
Breast and ovarian cancer Qualitative interviews -Reflecting on the past: the impact of a cancer diagnosis on self-identity -Looking to the future: genetic risk and identity -Accounting for the past and predicting the future: women's motivations for undergoing genetic testing -Intrusion -Avoidance Jones et al. (2018) [16] FH Qualitative interviews -Understanding of FH (i.e., the inherited nature of FH) -Concerns about increased risk for heart attacks -Confusion and uncertainty for future medical care -Importance of genetic test results for family members.
-Communicating with family members to understand family history of heart disease.
-Feelings of shock from incidental genetic test findings (i.e., non-paternity)  Breast and ovarian cancer Qualitative interviews -Still learning -Feeling vulnerable to an impending cancer diagnosis and pressure to act before crossing a threshold into territory perceived as unsafe -Making active lifestyle choices to support healthy living since learning their mutation status -Navigating to and through genetic counseling and/or testing and risk management decision making -Actively seeking readily accessible resources to clarify and facilitate risk management

Overall CASP Assessment
None of the studies that met the inclusion criteria were excluded following CASP appraisal, yet we observed some variation in their quality (see Table 6). Every study provided a clear statement of research aims, although only a third of the studies (n = 8) contained appropriate qualitative methodology largely because many of the studies reported qualitative PRO themes from quantitative PROM surveys. The majority of studies (n = 22) used a research design that was appropriate to address the research aims and research issue, with the exception of Jones et al. and Lee et al., whose research design was unclear or not clear enough to draw a distinct connection between the study aims and the methods [16,26]. Specifically, Jones et al. did not include details on qualitative data coding methods despite being mixed-methods studies [16]. Lee et al. did not report qualitative study methods, although they reported qualitative PRO results [26]. Every study used appropriate recruitment strategies.
One study (Croyle et al.) did not clearly describe the relationship between the researchers and study participants [20]. The authors did not acknowledge at the end of the report potential conflicts of interest, yet they noted a study limitation of sample bias and the likelihood of adverse psychological effects among individuals with varying levels of health knowledge and risk awareness. Every study reported rigorous data analysis, with the exception of Lee et al., whose study methods were not well-structured or unclear [26]. Despite these CASP assessment limitations, every study provided a clear statement of PRO findings, and most of the studies (n = 22) provided valuable knowledge around PROs following genetic testing for breast and ovarian cancer syndrome, Lynch syndrome, and/or FH.

Discussion
This systematic review examined two aspects of the existing literature on PROs following genetic testing for FH, breast and ovarian cancer syndrome, and Lynch syndrome: (1) qualitative themes within and among PROs and PROMs collected, measured, and reported to date; and (2) existing PRO/PROM collection methods and measures that, to date, have captured and described patient needs, perspectives, and personal utility.
Several PROM instruments were used across studies to measure and collect PROs along three overarching themes following genetic testing (see Table 3): (1) psychological, mood, emotional function or state (i.e., feelings of anxiety, depression, distress, regret, and worry); (2) knowledge and perceptions of their lifetime or genetic disease risk, uncertainty about managing their genetic disease risk, and health screening behaviors; and (3) coping style or mechanisms, social functioning and support, quality of life, genetic testing satisfaction, functional health, and medical outcomes.
Three themes were found across studies reporting PROs collected using general surveys (see Table 7): (1) self-regulation and decision making (e.g., utilization of riskmitigating procedures such as prophylactic surgery); (2) experience and satisfaction with the genetic testing process; and (3) distress, knowledge, and risk perception. Four themes were found across studies reporting qualitative PRO data (see Table 5): (1) feelings of satisfaction or readiness about future personal and family communication and planning; (2) genetic disease awareness and knowledge gain; (3) concern about insurance discrimination and stigmatization, as well as the cost of testing or care; (4) psychological and emotional feelings of intrusion, avoidance, shock, disbelief, distrust, curiosity, emotional coping, feeling emotional, psychosocial impact, relief, gratitude, regret, and fear.
PROs elements captured in this review that overlap with the personal utility elements described by Kohler et al. include coping, future planning and preparedness (family and personal), well-being and quality of life, knowledge gain, family communication, discrimination and stigma, and social support (see Table 8) [6]. The PRO themes and data collection methods identified in our review can inform engagement and consensus-or capacity-building initiatives that aim to (1) reconcile themes within the present literature review against the personal utility identified by Kohler et al. and possibly others; (2) build on the current literature to contextually define PROs following genetic testing for breast and ovarian cancer, Lynch syndrome, and FH; (3) determine if the themes identified are sufficient in substance or if more substance or exploration of themes are needed for further definition; and (4) channel these themes and definitions into real-world scenarios, data standards and collection methods, and other important practices or protocols moving forward.
Dobrozsi and Panepinto proposed a conceptual framework to incorporate PROs as measures that define patient symptoms and function with the goal of tailoring therapies, improving patient outcomes, improving patient-provider communication, and improving health care provider quality and performance [44]. By implementing this conceptual framework and describing and elucidating the role of PROs within the clinical context of genetic testing, it may become possible to understand the full value and personal utility of genetic testing for these conditions from the patient perspective. What is required in tandem, however, is more precision toward the adaptation or development of PROMs in this interventional context. As Victorson stated in a recent presentation outlining challenges to uses of PROs (e.g., poor validity, lack of sensitivity and specificity to specific interventions, low meaningfulness in certain contexts, and inappropriate survey/questionnaire delivery mechanisms), 'PROs are not without their challenges . . . All of these things are important considerations to consider when creating a new PRO measure' [45].
Indeed, PROs hold important implications for real-world clinical, research, market, reimbursement, and policy settings. PROs can inform and affect important and consequential areas of clinical practice and research, policy, pricing and reimbursement negotiations, and regulation concerning genetic testing for these conditions. For example, the PROs identified in this review can be cross-examined in current authoritative lists of validated PROMs, such as the (1) Patient-Reported Outcomes Measurement Information System, and (2) validated PROM list provided by the Australian Commission on Safety and Quality in Healthcare that covers high-burden cancers and cardiovascular diseases [46,47]. Additionally, PROs, being real-world evidence and clinical outcome assessment measures, informed the development of guidance documents focused on integrating patient experience data into drug and/or diagnostic test development processes (e.g., development processes for pharmacogenomic drugs and companion diagnostics). The drug development process mandated by the Prescription Drug User Fee Act VI (PDUFA VI) and Twenty-First Century Cures Act in the US is one such example that holds relevance [48]. Discussions have begun and continue today about how health authorities in France, the US, and the United Kingdom can integrate PROs, as a form of real-world evidence, into market authorization discussions and price and reimbursement negotiations [49,50].
In addition to analog surveys, interviews, and focus groups, PROs are and can be collected in both structured and unstructured data formats as digital measures. This can occur both within and outside of clinical settings using the internet or Internet of Things (IoT; e.g., data cloud hosts or servers), automated telephone systems, or downloadable applications such as mobile apps (digital PROs) [48,51,52]. There are benefits to collecting PROs digitally. For example, patients reporting digital PROs can report outcomes in realtime versus only during clinical appointments where there may be time and spatial and/or human resource challenges that might introduce confounding or other limitations into PRO data or collection methods.
There are risks, however, to the use and implementation of digital PROs following genetic testing, such as privacy and security risks in the event such PROs are collected and shared with third parties without patient awareness or consent. Privacy and security risks are especially concerning for patients reporting PROs following genetic testing, as such PROs can have implications for not just the patient but also their biological family members that may or may not be aware of the genetic condition being tested [53]. The sensitive and personal nature of PROs also renders PRO data vulnerable to re-identification if de-identified PRO data is shared with third parties. Novel approaches to collecting and analyzing structured and unstructured PRO data, such as the federated machine learning approach, can therefore be explored as potentially viable mechanisms for collecting digital PROs in a privacy-preserving manner following genetic testing [52].
There are three key limitations to our systematic literature review. First, our literature search was conducted in only three databases (PubMed/MEDLINE, EMBASE, and Yale University's TRIP Medical Database). Future reviews could repeat our search methodology in other existing databases. Second, given that our review focused on a qualitative assessment of PROs following genetic testing for breast and ovarian cancer syndrome, Lynch syndrome, and FH, our methodological quality assessment of each study was from a qualitative standpoint. Future research could involve a methodological quality assessment of studies, particularly for studies reporting quantitatively measured PROs. Finally, our overall findings reflect an overrepresentation of or bias toward studies reporting (1) PROs following genetic testing for breast and ovarian cancer and studies conducted in the USA, and (2) PROs from a majority of participants of White/Caucasian/Northern European/Anglo-Saxon descent. Further research should examine PROs following genetic testing for Lynch syndrome and FH within and outside of the USA to enrich our review findings. Additionally, given that 11 of the 24 studies that met our inclusion criteria reported a majority of participants of White/Caucasian/Northern European/Anglo-Saxon descent, future studies should collect and assess the scope and range of PROs following genetic testing in more racially and ethnically diverse populations. Lastly, recent PRO studies have described how the coronavirus disease 2019 (COVID-19) pandemic has negatively impacted the daily quality of life, mental health, and medical management of some cancer patients [54,55]. Therefore, future work should also examine, through PRO assessments, the intersectional impact of COVID-19 and genetic testing on breast and ovarian cancer syndrome, Lynch syndrome, and FH patients.

Conclusions
PROs are important data endpoints that can reflect or convey patient experiences, feelings, thoughts, and journeys across time and health settings. PRO data collection methods are, therefore, important and necessary to understand or perhaps even predict patient health beliefs, risks, and behaviors following genetic testing. This review presents the state of evidence regarding PRO data collection methods and themes following genetic testing for FH, breast and ovarian cancer, and Lynch syndrome and offers recommendations for future clinical and policy engagement and research. Clinicians, patients, regulators, policymakers, and other stakeholders are therefore encouraged to disseminate and implement these findings across key clinical, educational, and policy settings and discussions.