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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

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.

The increasing use of genetic testing for BRCA1/2 and other pathogenic variants in the management of women with breast and ovarian cancer necessitates increased genetic literacy in oncology healthcare professionals. This pilot study aimed to evaluate an online training program to increase genetic literacy and communication skills in Australian oncology healthcare professionals tasked with discussing and coordinating mainstream genetic testing with breast and ovarian cancer patients. A training website with embedded videos was developed. This study assesses the website's acceptability and user-friendliness; suggestions for improvement were also elicited. Oncology healthcare professionals were recruited through relevant professional organisations, invited to the study by email, asked to work through the website and then complete an online questionnaire. Thirty-two oncology healthcare professionals completed the questionnaire after viewing the website. Nearly all participants were satisfied with the information contained in the program (very satisfied: n = 14/32, 44%, satisfied: n = 17/32, 53%, neither satisfied nor dissatisfied: n = 1/32, 3%) and reported that they had gained new skills (n = 29/32, 91%) and had increased confidence (n = 29/31, 94%) in communicating with breast and ovarian cancer patients about genetic testing. More than 93% (28/30) of participants endorsed the online program as clearly presented, informative, relevant and useful. This pilot study demonstrated high feasibility and acceptability of the training program to increase genetic literacy and communication skills in oncology healthcare professionals discussing genetic testing with breast and ovarian cancer patients. Further evidence from a randomised trial is needed to evaluate effects on changing clinical practice, improving patient outcomes, and cost-effectiveness.Copyright © 2021, The Author(s), under exclusive licence to Springer Nature B.V.

Introduction: Polygenic risk scores (PRS) for breast cancer risk have emerged as a potential tool for informing disease risk management. However, little is known about women's responses to receiving this information. This study aimed to prospectively assess patient reported outcomes and risk management behavior of women choosing to receive (receivers) or decline (decliners) their breast cancer PRS. Method(s): Women either unaffected or affected by breast cancer and from families with no identified pathogenic variant in a breast cancer risk gene were invited to receive their PRS. Genotyping for 62 common variants was performed, from which a PRS and relative risk were calculated. All participants completed a questionnaire at study enrollment. Receivers completed questionnaires at two-weeks and 12- months after receiving their PRS, and decliners a second questionnaire at 12-months post study enrollment. Result(s): Of the 208 participants, 165 (79%) received their PRS. Among receivers there were no changes in anxiety or distress following testing. Receiving a low PRS was associated with reduced perceived breast cancer risk at 12-months (p = 0.030). At 12-months, breast screening and uptake of risk-reducing strategies were consistent with current Australian guidelines of breast cancer risk management. Compared to receivers, decliners reported significantly higher decisional regret regarding receipt of their PRS (p<0.001). Reasons for declining PRS included being unable to attend the appointment in person and concerns over potential emotional response. Conclusion(s): Our findings provide additional support for the suitability of PRS in clinical practice, while highlighting the issues that need to be addressed when providing this information.

AbstractGermline 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 res

Carriers of germline mutations in genes associated with Lynch syndrome are at increased risk for colorectal, endometrial, ovarian, and other cancers. There is evidence that daily consumption of aspirin may reduce cancer risk in these individuals. There is a need for educational resources to inform carriers of the risk-reducing effects of aspirin or to support decision-making. An educational leaflet describing the risks and benefits of using aspirin as risk-reducing medicine in carriers of Lynch-syndrome-related mutations is developed and pilot tested in 2017. Carriers are ascertained through a familial cancer clinic and surveyed using a mailed, self-administered questionnaire. The leaflet is highly rated for its content, clarity, length, relevance, and visual appeal by more than 70% of the participants. Most participants (91%) report "a lot" or "quite a bit" of improvement in perceived understanding in knowledge about who might benefit from taking aspirin, its benefits, how long to take it, the reduction in bowel cancer risk, and the optimal dosage. A few (14%) participants seek more information on the dosage of aspirin. This leaflet will be useful as an aid to facilitate discussion between patients and their health care professionals about the use of aspirin as a risk-reducing medication.

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.

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

OBJECTIVE: To understand advanced cancer patients' experience of uncertainty when receiving comprehensive tumor genomic profiling (CTGP) results, and their perceptions of how healthcare provider (HCP) communication impacts uncertainty. METHODS: Thirty-seven semi-structured interviews with advanced cancer patients were conducted within two weeks of patients receiving CTGP results. Transcripts were thematically analyzed, using an inductive approach. RESULTS: We identified three themes that illustrate patient experience of uncertainties when receiving CTGP results: 1. Type and degree of uncertainty fluctuates along with changing illness circumstances and the nature of the CTGP results; 2. HCPs' co-ordination of care and communication shapes uncertainty, with immediate, clearer and simpler information promoting certainty; and 3. Patients felt that communicating results to reduce relatives' uncertainty is important, with patients choosing the time and process for achieving this and desiring HCPs support. CONCLUSION: Oncology patients are confronted with an array of uncertainties. Clear, simple communication from HCPs about results and their implications, and support to manage uncertainty, will be of benefit. PRACTICE IMPLICATIONS: If CTGP is to become routine clinical practice, clear communication will be crucial in reducing uncertainty. Awareness of potential uncertainties experienced by patients when receiving results, will assist HCPs to address uncertainties, reduce uncertainty where possible, and offer targeted support to patients struggling with uncertainty.

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.

Genomic Sequencing (GS) to identify high cancer risk will soon enter clinical practice at significant cost to the health system. This study aimed to quantify perceived value of GS to Australian cancer patients and their first-degree relatives participating in a genomic sequencing study, and factors associated with value. Participants were recruited upon consent to the genomics study. Eligible participants (with cancer of likely genetic etiology, or a first-degree relative) completed a questionnaire prior to GS. Willingness to pay was assessed via hypothetical trade-off scenarios of actionable result return rates of 1%, 10%, 20%, 30%, 40% or 50%. Of 348 probands and 213 relatives (92% and 93% response rate), 81% would consistently have GS for as little as a 1% actionable return rate. Participants would pay a median of $1,000 for return rates of at least 20% (probands) or 30% (relatives), and $300 for lower return rates. Probands with common cancers and negative attitudes to uncertainty were more likely to have GS; those with higher education were more willing to pay $1,000 and $3,000 for lower return rates. This study found high interest in, but lower willingness to pay for GS in cancer patients and their first-degree relatives, possibly due to inability to pay. Further research is needed to improve our understanding of how individuals in different risk circumstances, trade-off the risks, harms, and benefits of GS.

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.

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.