Family communication and results disclosure after germline sequencing: A mixed methods study.

OBJECTIVE: Research on family communication of germline genome sequencing (GS) results (versus of genetic results after targeted genetic testing) is still emerging, yet potentially complex results increase the importance of communicating risk to relatives. Promoting equity by ensuring patients have sufficient health literacy to interpret results is important in this context. This study aimed to identify cancer patients' perceived importance of result disclosure, predictors of perceptions, and perspectives on family communication. METHODS: This explanatory-sequential, cross-sectional mixed-methods study involved participants (n = 246) completing a questionnaire and (n = 20) a semi-structured interview. Ordinal logistic regressions determined associations between potential predictors and perceived importance of result disclosure. Interview transcripts were analysed thematically using a constant-comparative approach. RESULTS: More participants intended disclosing to nuclear (77.4%) than to extended family (42.7%). More than half (59.3%) felt results were family information; 62.7% believed it was important to disclose results to family members. Nuclear and extended family communication scores and education level were significantly positively associated with perceived importance of disclosure (p < 0.05). Six qualitative themes were identified: i) Responsibility to inform, ii) Choice, iii) Autonomy, iv) Family Communication, v) Significance of results, and vi) Health professional role. CONCLUSION: Low health literacy and family conflict can complicate communication of GS results. Patients seek clear, interpretable information in a format they can easily communicate. PRACTICE IMPLICATIONS: Healthcare professionals can facilitate discussion of GS results by offering written information, encouraging disclosure, exploring existing family dynamics and communication patterns, and offering strategies to improve family communication. Centralised genetic communication offices and chatbots can also be helpful.

Health professionals' role in the transfer of mosaic embryos after preimplantation genetic testing for aneuploidies.

RESEARCH QUESTION: What are health professionals' clinical practices, views and self-rated competencies regarding the transfer of mosaic embryos? DESIGN: This was a cross-sectional study using surveys. RESULTS: Data were collected from the Royal Australian and New Zealand College of Obstetricians and Gynaecologists and the Fertility Society of Australia and New Zealand. Ninety-five responses were analysed and reported. The results show that most health professionals (n = 62) discussed the transfer of mosaic embryos for different reasons and raised concerns regarding various risks. Although many health professionals were unsure whether mosaic embryos should be transferred, they were more inclined to encourage transfer if the scenario involved segmental losses compared with mosaicism involving duplication of the entire chromosome (i.e. trisomy 21) (e.g. OR = 0.21, P < 0.001; OR = 2.78, P = 0.04). The majority of health professionals would inform patients about the mosaicism to facilitate informed decision making. The factor that health professionals identified as most important when discussing the transfer of mosaic embryos was the specific chromosome involved. Different self-rated competencies were found among health professionals with different backgrounds. Geneticists and genetic counsellors had the highest self-rated competencies. CONCLUSIONS: Most health professionals were willing to discuss the mosaicism in the embryo with patients to facilitate informed decision making. However, health professionals' uncertainty towards the transfer of mosaic embryos indicated a lack of a standardized transfer policy. In addition, obstetricians, gynaecologists and those with multiprofessional backgrounds showed deficiencies in several self-rated competencies, suggesting that education targeted to these groups is needed to optimize the quality of care of women considering transfer of mosaic embryos.

Exploring the impact of the reclassification of a hereditary cancer syndrome gene variant: emerging themes from a qualitative study.

The complexity of genetic variant interpretation means that a proportion of individuals who undergo genetic testing for a hereditary cancer syndrome will have their test result reclassified over time. Such a reclassification may involve a clinically significant upgrade or downgrade in pathogenicity, which may have significant implications for medical management. To date, few studies have examined the psychosocial impact of a reclassification in a hereditary cancer syndrome context. To address this gap, semi-structured telephone interviews were performed with eighteen individuals who had a BRCA1, BRCA2 or Lynch syndrome-related (MLH1, MSH2, MSH6 or PMS2) gene variant reclassified. The interviews were analysed utilising an inductive, qualitative approach and emergent themes were identified by thematic analysis. Variable levels of recall amongst participants were found. Common motivations for initial testing included a significant personal and/or family history of cancer and a desire to "find an answer". No individual whose uncertain result was upgraded reported negative psychosocial outcomes; most reported adapting to their reclassified result and appraised their genetic testing experience positively. However, individuals whose likely pathogenic/pathogenic results were downgraded reported feelings of anger, shock and sadness post reclassification, highlighting that additional psychosocial support may be required for some. Genetic counselling issues and recommendations for clinical practice are outlined.

Population-based BRCA1/2 testing programmes are highly acceptable in the Jewish community: results of the JeneScreen Study.

BACKGROUND: Ashkenazi Jewish (AJ) people have a higher incidence of BRCA1/2 pathogenic variants (PVs) than unselected populations. Three BRCA-Jewish founder mutations (B-JFMs) comprise >90% of BRCA1/2 PVs in AJ people. Personal/family cancer history-based testing misses ≥50% of people with B-JFM. METHODS: We compared two population-based B-JFM screening programmes in Australia-using (1) an online tool (Sydney) and (2) in-person group sessions (Melbourne). RESULTS: Of 2167 Jewish people tested (Sydney n=594; Melbourne n=1573), 1.3% (n=28) have a B-JFM, only 2 of whom had a significant cancer family history (Manchester score ≥12). Pretest anxiety scores were normal (mean 9.9±3.5 (6-24)), with no significant post-result change (9.5±3.3). Decisional regret (mean 7.4±13.0 (0-100)), test-related distress (mean 0.8+/2.2 (0-30)) and positive experiences (reverse-scored) (mean 3.4±4.5 (1-20)) scores were low, with no significant differences between Sydney and Melbourne participants. Post-education knowledge was good overall (mean 11.8/15 (±2.9)) and significantly higher in Melbourne than Sydney. Post-result knowledge was the same (mean 11.7 (±2.4) vs 11.2 (±2.4)). Participants with a B-JFM had higher post-result anxiety and test-related distress and lower positive experiences, than those without a B-JFM, but scores were within the normal range. Family cancer history did not significantly affect knowledge or anxiety, or pretest perception of B-JFM or cancer risks. Most participants (93%) were satisfied/very satisfied with the programme. CONCLUSION: Both B-JFM screening programmes are highly acceptable to Australian Jewish communities. The programme enabled identification of several individuals who were previously unaware they have a B-JFM, many of whom would have been ineligible for current criteria-based testing in Australia.

Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort.

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies.

Which Test Is Best? A Cluster-Randomized Controlled Trial of a Risk Calculator and Recommendations on Colorectal Cancer Screening Behaviour in General Practice.

INTRODUCTION: This cluster-randomized controlled trial aimed to assess the effect of the "Which test is best?" tool on risk-appropriate screening (RAS) and colorectal cancer (CRC) screening uptake. METHODS: General practices in Sydney and Melbourne, Australia, and a random sub-sample of 460 patients (aged 25-74 years) per practice were invited by post. Clusters were computer randomized independently of the researchers to an online CRC risk calculator with risk-based recommendations versus usual care. Primary and secondary outcomes were RAS and screening uptake via self-reported 5-year screening behaviour after 12 months follow-up. The usual care group (UCG) also self-reported 5-year CRC screening behaviour at 12 month post-randomization. RESULTS: Fifty-six practices were randomized (27 to the intervention and 29 to the control, 55 practices participated) with 818 intervention and 677 controls completing the primary outcome measure. The intervention significantly increased RAS in high-risk participants compared with UCG (80.0% vs. 64.0%, respectively; OR = 3.14, 95% CI: 1.25-7.96) but not in average-risk (44.9% vs. 49.5%, respectively; OR = 0.97, 95% CI: 0.99-1.12) or moderate-risk individuals (67.9% vs. 81.1%, respectively; OR = 0.40, 95% CI: 0.12-1.33). Faecal occult blood testing uptake over 12 months was increased compared with the UCG (24.9% vs. 15.1%; adjusted OR = 1.66, 95% CI: 1.24-2.22), and there was a non-significant increase in colonoscopies during the same period (16.6% vs. 12.2%; adjusted OR = 1.42, 95% CI: 0.97-2.08). CONCLUSION: An online CRC risk calculator with risk-based screening recommendations increased RAS in high-risk participants and improved screening uptake overall within a 12-month follow-up period. Such tools may be useful for facilitating the uptake of risk-based screening guidelines.

Exploration of decision-making regarding the transfer of mosaic embryos following preimplantation genetic testing: a qualitative study.

STUDY QUESTION: What are patients' reasoning and decisional needs in relation to the transfer of mosaic embryos following preimplantation genetic testing (PGT)? SUMMARY ANSWER: This study identified four themes, which were patients' reasoning behind decision-making, their decisional needs, the influence of the mosaic embryos on the decision-making and the role of health professionals. WHAT IS KNOWN ALREADY: To date, no study has investigated the reasoning of patients behind their decision-making and the influence of mosaic embryos. STUDY DESIGN SIZE DURATION: This is a cross-sectional study using a qualitative approach. Twenty participants were interviewed, and recruitment was ceased when no new information was identified in the data analysis. It ensured a sufficient sample size for a qualitative study. PARTICIPANTS/MATERIALS SETTING METHODS: Participants were females with mosaic embryos. Semi-structured in-depth interviews were conducted via telephone. MAIN RESULTS AND THE ROLE OF CHANCE: Four themes were identified: reasoning behind decision-making, decisional needs, influence of mosaic embryos on decision-making and the role of health professionals. Potential risks of transferring mosaic embryos and prioritization of euploid embryos were the main reasons for not transferring mosaic embryos. A lack of alternatives, perceived benefits and risk tolerance were main reasons for transferring mosaic embryos. Patients reported that information on mosaic embryos, amniocentesis and termination was important to support their decision-making. Unmet needs relating to healthcare services and social support were reported. In addition, having mosaic embryos affected the patients' emotional and behavioural responses, discussions about prenatal testing, attitudes to termination and further IVF cycles and attitudes towards PGT. Health professionals were found to influence the patients' decision-making. LIMITATIONS REASONS FOR CAUTION: Participants were recruited through one clinic, which may limit the transferability of results. Also, patients' experiences in relation to financial aspects of PGT may not be relevant to other jurisdictions due to different healthcare policies. WIDER IMPLICATIONS OF THE FINDINGS: The results may inform how clinicians provide healthcare services based on factors influencing patients' decision-making. Health professionals should be aware of the influence their attitudes can have on patients' decision-making and should present information accordingly. Also, providing all relevant information may help to facilitate informed decision-making. Provision of psychological support from professionals and support groups is also critical during the process of testing and transfer. Patients have educational needs regarding mosaic embryos, and educational resources including decision aids in plain language are needed. STUDY FUNDING/COMPETING INTERESTS: B.M. was funded through a Senior Research Fellowship Level B (ID 1078523) from the National Health and Medical Research Council of Australia. L.C. was supported by a University International Postgraduate Award under the Australian Government Research Training Program (RTP) scholarship. No other funding was received for this study. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Factors influencing patients' decision-making about preimplantation genetic testing for monogenic disorders.

STUDY QUESTION: What are the roles of individual and interpersonal factors in couples' decision-making regarding preimplantation genetic testing for monogenic disorders (PGT-M)? SUMMARY ANSWER: Couples' decision-making regarding PGT-M was associated with individual and interpersonal factors, that is the perceived consistency of information received, satisfaction with information, self-efficacy (individuals' beliefs in their ability to make decisions), actual knowledge about PGT-M and social support from the partner. WHAT IS KNOWN ALREADY: Various factors have been shown to be associated with decision-making regarding PGT-M. However, PGT-M is experienced at an individual level, and to date, no studies have investigated the roles of the above-mentioned individual and interpersonal factors. STUDY DESIGN, SIZE, DURATION: This is a cross-sectional study with 279 participants. Participants were recruited through IVFAustralia, Sydney Children's Hospital and support groups from May 2020 to November 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants were women who had undergone or were considering PGT-M and their partners. Participants were recruited through IVFAustralia, Sydney Children's Hospital and support groups to complete online questionnaires. Decisional regret, decisional satisfaction and decisional conflict were measured as outcome variables. Multiple linear regressions were performed to examine the association between factors and outcome variables. Mann-Whitney U tests were performed to test the differences between participants who had undergone PGT-M and those who were considering PGT-M. MAIN RESULTS AND THE ROLE OF CHANCE: For couples who had undergone PGT-M, decisional regret was significantly negatively associated with perceived consistency of information received (ß = -0.26, P < 0.01), self-efficacy (ß = -0.25, P < 0.01) and actual knowledge about PGT-M (ß = -0.30, P < 0.001), while decisional satisfaction had positive association with satisfaction with information received (ß = 0.37, P < 0.001) and self-efficacy (ß = 0.24, P < 0.05). For couples who were considering PGT-M, decisional conflict was negatively associated with satisfaction with information received (ß = -0.56, P < 0.001). For females who had undergone PGT-M, decisional regret was negatively associated with social support from the partner (ß = -0.35, P < 0.05) in addition to perceived consistency of information received (ß = -0.24, P < 0.05). In this group, decisional satisfaction was positively associated with women's satisfaction with the information received (ß = 0.34, P < 0.01), social support from the partner (ß = 0.26, P < 0.05) and self-efficacy (ß = 0.25, P < 0.05). For females who were considering PGT-M, decisional conflict was negatively associated with satisfaction with the information received (ß = -0.43, P < 0.01) and social support from the partner (ß = -0.30, P < 0.05). This study also identified those aspects of PGT-M that couples felt most concerned about in relation to their decision-making, in particular safety issues such as short- or long-term health problems for the baby and potential harms to the embryos and the mother's health. The likelihood of getting pregnant and having a baby with a genetic condition being tested for were also important in couples' decision-making. LIMITATIONS, REASONS FOR CAUTION: This study assessed the concerns of couples about having a baby with a variety of genetic conditions. However, condition-specific issues might not be covered. Furthermore, social support from the partner was assessed among females only. Male participants' perceived social support from their partner and the association between mutual support and decision-making were not assessed due to the absence of dyadic data. WIDER IMPLICATIONS OF THE FINDINGS: Results highlight the importance of effective patient education on PGT-M and the need to provide high-quality and consistent information in the context of patient-centred care. Patients are likely to benefit from information that addresses their specific concerns in relation to PGT-M. From females' perspective, support from partners is essential, and partners should, therefore, be encouraged to participate in all stages of the decision-making process. Suggestions for future studies were made. STUDY FUNDING/COMPETING INTEREST(S): B.M. was funded through a Senior Research Fellowship Level B (ID 1078523) from the National Health and Medical Research Council of Australia. L.C. was supported by a University International Postgraduate Award under the Australian Government Research Training Program (RTP) scholarship. No other funding was received for this study. The authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Concerns about the use of polygenic embryo screening for psychiatric and cognitive traits.

Private companies have begun offering services to allow parents undergoing in-vitro fertilisation to screen embryos for genetic risk of complex diseases, including psychiatric disorders. This procedure, called polygenic embryo screening, raises several difficult scientific and ethical issues, as discussed in this Personal View. Polygenic embryo screening depends on the statistical properties of polygenic risk scores, which are complex and not well studied in the context of this proposed clinical application. The clinical, social, and ethical implications of polygenic embryo screening have barely been discussed among relevant stakeholders. To our knowledge, the International Society of Psychiatric Genetics is the first professional biomedical organisation to issue a statement regarding polygenic embryo screening. For the reasons discussed in this Personal View, the Society urges caution and calls for additional research and oversight on the use of polygenic embryo screening.

What is the effect of a low literacy talking book on patient knowledge, anxiety and communication before radiation therapy starts? A pilot study.

INTRODUCTION: Radiation therapy is a common cancer treatment, requiring timely information to help patients prepare for treatment. We pilot tested a low literacy, psycho-educational talking book (written booklet, with accompanying audio recording) to examine (i) the effect of the tool on knowledge, anxiety and communication; (ii) acceptability, and (iii) how it was used in appointments. METHODS: A pre-post design was employed. Patients scheduled to receive radiation therapy for any cancer were recruited from two hospitals in Sydney, Australia. Participants were sent the talking book before treatment planning and completed baseline and follow-up surveys, before and after the intervention. RESULTS: Forty participants were recruited, and 39 completed all study assessments. Overall, knowledge increased after receiving the talking book by 3.8 points from 13.9 to 17.7/20 (95% confidence interval (CI) 2.7, 4.8, P < 0.001). Anxiety and concerns were significantly lower after receiving the talking book (P = 0.015 and P = 0.004, respectively). Nearly half of participants (s = 17, 48%) reported using the book during appointments. Most reported finding it easier to communicate (n = 31, 89%) and to ask more questions (n = 21, 62%). CONCLUSION: The talking book shows promise in improving knowledge, reducing anxiety and enhancing communication. Strategies to support the implementation of the talking book are required. Further studies to translate the book into different languages are also planned.

Psychological outcomes in advanced cancer patients after receiving genomic tumor profiling results.

BACKGROUND: Comprehensive tumor genomic profiling (CGP) offers hope for personalized treatment for cancer patients when other treatment options have been exhausted. However, receipt of nonactionable or ambiguous results could be an ongoing source of distress. We investigated patterns of hope, anxiety, depression, and CGP-specific anxiety in advanced cancer patients after receiving CGP results and 2-3 months later. METHOD: Participants were enrolled in a longitudinal psychosocial substudy, embedded in the Molecular Screening and Therapeutics Program, and had advanced solid cancers of any histological type with sufficient and accessible tissue for CGP. At T0 (before receiving CGP results), 1,431 participants completed sociodemographic, disease and psychosocial measures. At T1 (1-4 weeks after receiving CGP results) and T2 (2-3 months post-T1), 374 participants completed psychological outcome measures. Predictors of outcomes at T2 were identified using multinomial logistic regression. RESULTS: Approximately 75% of participants did not experience significant hopelessness or distress at T1 and T2. Hope decreased by T2, yet general anxiety and CGP-specific anxiety also decreased. Receiving actionable results did not impact psychological outcomes at T2. At T2, lower hope, and higher anxiety, depression and CGP-specific anxiety were associated with lower self-efficacy. Psychological and demographic factors (age, socioeconomic status, language, medical occupation, urban living, family history of cancer) independently predicted one or more psychological trajectories. Worse health status and perceived susceptibility to cancer progression predicted hope and anxiety trajectories. CONCLUSION: Further research on interventions to best support patients undergoing CGP with high anxiety, hopelessness, fear of cancer progression, and poorer health is urgently needed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Perceptions of causal attribution and attitudes to genetic testing among people with schizophrenia and their first-degree relatives.

Rapid advances in the genetics of psychiatric disorders mean that diagnostic and predictive genetic testing for schizophrenia risk may one day be a reality. This study examined how causal attributions for schizophrenia contribute to interest in a hypothetical genetic test. People with schizophrenia and first-degree relatives of people with schizophrenia were recruited through a schizophrenia research bank and mental health organisation. Semi-structured telephone interviews were conducted with 13 individuals with schizophrenia and 8 first-degree relatives. Transcripts were subjected to a qualitative analysis using the thematic analysis framework. Five themes were developed: (i) "It is like a cocktail", with most participants aware that both genetic and environmental factors contributed to causation, and many mentioning the positive impact of genetic causal explanations; (ii) "Knowledge is power" (i.e., in favour of genetic testing); (iii) Genetic testing provides opportunities for early intervention and avoiding triggers, with participants citing a wide range of perceived benefits of genetic testing but few risks; (iv) Views on reproductive genetic testing for schizophrenia risk with a few participants viewing it as "playing God" but not necessarily being against it; and (v) "It snowballs", whereby participants' understanding of genetics was sophisticated with most believing that multiple rather than single genes contributed to schizophrenia. In conclusion, many individuals had a sound understanding of the role of genetic testing if it were to become available, with evidence of insight into the role of multiple genes and the contribution of other risk factors that may interact with any inherited genetic risk.

Psychological predictors of cancer patients' and their relatives' attitudes towards the return of genomic sequencing results.

This study assessed the psychological predictors of attitudes toward the return of germline genomic sequencing results in cancer patients and their biological relatives with a likely genetic basis for their cancer diagnosis, who completed a questionnaire prior to undergoing genomic sequencing. Of 602 probands and relatives, 94% of probands and 89% of relatives thought people would like to be informed about single-gene conditions for which there is prevention or treatment. Amongst relatives, this view was associated with higher perceived susceptibility and self-efficacy. Probands (66%) and relatives (59%) thought people would be interested in learning about single-gene conditions for which there is no prevention or treatment. Amongst probands, this view was associated with lower tolerance of uncertainty and amongst relatives with higher self-efficacy. Probands (92%) and relatives (90%) thought people would like to be informed about polygenic conditions that can have a major impact on health. Amongst probands this view was associated with lower perceived susceptibility of cancer recurrence, and amongst relatives, with higher perceived susceptibility and self-efficacy. Probands (86%) and relatives (86%) thought that people would like to be informed about polygenic conditions that can have a lower impact on health, and this view was associated with a lower perceived susceptibility of recurrence amongst probands. In conclusion, these findings show that individuals' attitudes about the return of results depend on the perceived utility of different types of tests. Therefore, individuals need to gain a clear understanding of test utility, and appropriate consent processes are required to achieve informed choices.

Preferences for return of germline genome sequencing results for cancer patients and their genetic relatives in a research setting.

Germline genome sequencing (GS) holds great promise for cancer prevention by identifying cancer risk and guiding prevention strategies, however research evidence is mixed regarding patient preferences for receiving GS results. The aim of this study was to discern preferences for return of results by cancer patients who have actually undergone GS. We conducted a mixed methods study with a cohort of cancer probands (n = 335) and their genetic relatives (n = 199) undergoing GS in a research setting. Both groups completed surveys when giving consent. A subset of participants (n = 40) completed semi-structured interviews. A significantly higher percentage of probands thought people would like to be informed about genetic conditions for which there is prevention or treatment that can change cancer risk compared to conditions for which there is no prevention or treatment (93% [311] versus 65% [216]; p < 0.001). Similar results were obtained for relatives (91% [180] versus 61% [121]; p < 0.001). Themes identified in the analysis of interviews were: (1) Recognised benefits of GS, (2) Balancing benefits with risks, (3) Uncertain results are perceived as unhelpful and (4) Competing obligations. While utility was an important discriminator in what was seen as valuable for this cohort, there was a variety of responses. In view of varied participant preferences regarding return of results, it is important to ensure patient understanding of test validity and identify individual choices at the time of consent to GS. The nature and value of the information, and a contextual understanding of researcher obligations should guide result return.

Decisional needs of patients considering preimplantation genetic testing: a systematic review.

This systematic review reports on the needs and sources of support in patients' decision-making regarding the uptake of preimplantation genetic testing (PGT). Five databases were searched systematically to capture qualitative and quantitative studies. A total of 2336 studies were screened by title and abstract. Twelve studies met the eligibility criteria and reported on 4047 participants. This systematic review shows that patients need information directly relevant to PGT treatment, and information on health care relating to treatment and alternative reproductive options. Information that is too detailed, excessive and contains a large volume of medical terminology can be a barrier to decision-making. Published research suggests that health professionals provide general information on PGT and discuss it in detail only when patients require more information about it. Additionally, studies have shown that patients receive decisional support through mass media, significant persons in their lives and health professionals, whereas referring obstetricians and gynaecologists provided relatively less help compared with other health professionals. This systematic review highlights the importance of developing decision aids that meet patients' decisional needs as indicated in previous studies and that use innovative formats to deliver information. Additionally, given rapid technical developments, a dearth of continuing professional education is available on PGT for clinicians to keep updated.

Psychological impact of comprehensive tumor genomic profiling results for advanced cancer patients.

OBJECTIVE: Comprehensive tumor genomic profiling (CTGP) is increasingly used to personalize treatments, providing hope, but potentially disappointment, for patients. We explored psychological outcomes in patients with advanced, incurable cancer, after receiving CTGP results. METHODS: Participants with advanced, incurable cancer (n = 560, mean age 56, 43% university educated) in this longitudinal substudy of the Molecular Screening and Therapeutics Program (MoST), completed questionnaires before and after receiving CGP results. MoST participants, recruited from Australian oncology clinics, undergo CTGP, and if there are actionable findings, are offered treatment in a related therapeutic trial if available. RESULTS: Patients who received actionable results, (n = 356, 64%) had lower gene-related distress (MICRA) (p < 0.001) and Impact of Events scores (p = 0.039) than patients with non-actionable results. Those with actionable results offered ensured access to tailored treatment (n = 151) reported lower anxiety (p = 0.002) and depressive symptoms (p = 0.01) and greater hope (p = 0.002) than those not offered. Positive attitudes towards uncertainty and higher self-efficacy for coping with results were associated with lower psychological distress and uncertainty, and higher hope and satisfaction with the decision to have CTGP (ps=0.001-0.047). Those with higher knowledge reported greater anxiety (p = 0.034). CONCLUSION: Receiving a non-actionable CTGP result, or an actionable result without ensured access to treatment, may cause increased distress in advanced cancer patients. Coping style was also associated with distress. PRACTICE IMPLICATIONS: Pre-testing assessment and counseling addressing attitudes toward uncertainty and self-efficacy, and post-CTGP result support for patients receiving a non-actionable result or who receive an actionable results without ensured access to treatment, may benefit patients.

Polygenic risk in familial breast cancer: Changing the dynamics of communicating genetic risk.

Hereditary breast cancer is associated with known genetic changes: either variants that affect function in a few rare genes or an ever-increasing number of common genomic risk variants, which combine to produce a cumulative effect, known as a polygenic risk (PR) score. While the clinical validity and utility of PR scores are still being determined, the communication of PR is a new challenge for genetic health professionals. This study investigated how PR scores are discussed in the familial cancer clinic compared with a previous study assessing the communication of monogenic risk (MR) for breast cancer. Sixty-five PR consultations between genetic health professionals and women at familial risk of breast cancer were audiotaped, transcribed, and coded using a methodology adapted from the MR study. Analysis of consultations shows that while there were similarities in communicating MR and PR, the complexity and novelty of the polygenic information influenced the style of counseling used by genetic health professionals toward a teaching model of genetic counseling, rather than a patient-centered approach. In particular, compared to MR consultations, in PR consultations significantly fewer counselees (a) were asked about their reasons for attending genetic counseling; or (b) had their information preferences, decision-making style, medical knowledge, understanding, or concerns checked. In conclusion, it is anticipated that PR scores will become part of standard clinical practice. Thus, it will be important for all genetic health professionals to be appropriately educated so that they can tailor their communication to meet patient needs.

The impact of Marfan syndrome on an Aboriginal Australian family: 'I don't like it as much as I don't like cancer'.

Marfan syndrome (MFS) is an autosomal dominantly inherited connective tissue disorder. Aortic dilatation/dissection and ectopia lentis are the most severe features, which affect physical functioning and psychological well-being. In Aboriginal Australians, there is little psychosocial research on genetic conditions. This study explored the physical, psychological, and practical impacts of MFS on Aboriginal Australians. Eighteen (8 affected and 10 unaffected) members of a large Aboriginal Australian family with MFS participated in an ethically approved study. Semi-structured qualitative interviews were conducted, transcribed verbatim, and analyzed thematically. All individuals reported challenges from MFS, negatively affecting day-to-day living. Severe vision impairment was perceived as the greatest challenge, contributing to feelings of stigma and exclusion. With aging, concerns shifted toward cardiac complications. The unpredictability of lens dislocation and aortic dissection was reported to be psychologically challenging. Participants described MFS-related barriers to obtaining and retaining employment, especially following cardiac surgery; with consequential psychological and financial hardships. Participants articulated that their cultural drive to support the ill and respectfully mourn the deceased, regardless of distance, resulted in a significant financial burden. Additionally, when hospitalization and/or funerals occurred, financially solvent individuals were expected to share resources, without any expectation of repayment or reciprocity (i.e., 'demand sharing', common in Aboriginal Australian culture). This study documents the nature and pervasiveness of uncertainty for both affected and unaffected members of an MFS family. Many reported challenges are consistent with other MFS cohorts (including stigma, social exclusion, and unemployment). However, our findings suggest that cultural values may exacerbate the financial costs of MFS for Aboriginal Australians.

Stakeholder attitudes towards establishing a national genomics registry of inherited cancer predisposition: a qualitative study.

This study aimed to describe the acceptability and perceived barriers and enablers to establish a national registry targeting carriers of pathogenic variants in cancer susceptibility genes from stakeholders' perspectives. Such a registry may effectively target carriers to translate existing research findings into optimised clinical care and provide a population-level resource for further clinical research and new gene and therapy discovery. In-depth interviews were conducted with individuals from four stakeholder groups: carriers of pathogenic variants, healthcare professionals, data custodians from the field of familial cancer, and heads of molecular pathology laboratories. Interview data were subjected to a qualitative analysis guided by a thematic analysis framework using NVivo software. A total of 28 individuals were interviewed: 11 carriers, 8 healthcare professionals, 5 laboratory heads, and 4 data custodians. All carriers and healthcare professionals were enthusiastic about the potential research applications of the registry. Carriers described that altruistic motivations provided the foundation of their support of the planned registry. Some carriers felt comfortable with a broad consent (consenting once, prospectively), while others preferred a narrow consent approach (consenting each time data is accessed). Some carriers and data custodians and registry developers also expressed a reluctance to link family member data without appropriate consent. Participants' enthusiasm and support for a national registry herald a productive and responsive research partnership once the registry has been established. Participants' views can be used to inform the approaches to be taken to develop and manage such a registry as an implicit codesign approach.

Cancer patient knowledge about and behavioral intentions after germline genome sequencing.

OBJECTIVES: Germline genome sequencing (GS) is becoming mainstream in cancer diagnosis and risk management. Identifying knowledge gaps and determinants of health behavior change intentions will enable effective targeting of educational and management strategies to translate genomic findings into improved cancer outcomes. METHODS: Probands diagnosed with cancer of likely genetic origin that consented to but not yet undergone GS, and their biological relatives, completed a cross-sectional questionnaire assessing GS knowledge and hypothetical intention to change behaviors. RESULTS: Probands (n = 348; 57% university educated) and relatives (n = 213; 38% university educated) had moderate GS knowledge levels, with greater knowledge associated with higher education. Both populations reported high behavioral change intentions, significantly associated with being female (p = 0.01) and greater perceived importance of GS (p < 0.001), and for probands: being from English-speaking households (p = 0.003), higher socio-economic status (p = 0.01) and greater self-efficacy (p = 0.02). CONCLUSIONS: Increasing GS knowledge will enable realistic participant expectations surrounding germline GS. Actual behavior change should be monitored to determine whether increased cancer risk knowledge results in altered cancer-related behavior and ultimately, cancer outcomes. PRACTICE IMPLICATIONS: Educational resources should target specific populations to ensure informed decision-making and expectation management. Support tools facilitating and maintaining behavioral change may be needed to achieve improved cancer patient outcomes.