Universal genetic testing for women with newly diagnosed breast cancer in the context of multidisciplinary team care.

OBJECTIVE: To determine the feasibility of universal genetic testing of women with newly diagnosed breast cancer, to estimate the incidence of pathogenic gene variants and their impact on patient management, and to evaluate patient and clinician acceptance of universal testing. DESIGN, SETTING, PARTICIPANTS: Prospective study of women with invasive or high grade in situ breast cancer and unknown germline status discussed at the Parkville Breast Service (Melbourne) multidisciplinary team meeting. Women were recruited to the pilot (12 June 2020 - 22 March 2021) and expansion phases (17 October 2021 - 8 November 2022) of the Mutational Assessment of newly diagnosed breast cancer using Germline and tumour genomICs (MAGIC) study. MAIN OUTCOME MEASURES: Germline testing by DNA sequencing, filtered for nineteen hereditary breast and ovarian cancer genes that could be classified as actionable; only pathogenic variants were reported. Surveys before and after genetic testing assessed pilot phase participants' perceptions of genetic testing, and psychological distress and cancer-specific worry. A separate survey assessed clinicians' views on universal testing. RESULTS: Pathogenic germline variants were identified in 31 of 474 expanded study phase participants (6.5%), including 28 of 429 women with invasive breast cancer (6.5%). Eighteen of the 31 did not meet current genetic testing eligibility guidelines (probability of a germline pathogenic variant ≥ 10%, based on CanRisk, or Manchester score ≥ 15). Clinical management was changed for 24 of 31 women after identification of a pathogenic variant. Including 68 further women who underwent genetic testing outside the study, 44 of 542 women carried pathogenic variants (8.1%). Acceptance of universal testing was high among both patients (90 of 103, 87%) and clinicians; no decision regret or adverse impact on psychological distress or cancer-specific worry were reported. CONCLUSION: Universal genetic testing following the diagnosis of breast cancer detects clinically significant germline pathogenic variants that might otherwise be missed because of testing guidelines. Routine testing and reporting of pathogenic variants is feasible and acceptable for both patients and clinicians.

Assessing the acceptability, feasibility, and usefulness of a psychosocial screening tool to patients and clinicians in a clinical genetics service in Australia.

Increasing demand for clinical genetic services may impact the resources and quality of genetic counseling, potentially impacting patient outcomes. Using a psychosocial screening tool may aid the provision of genetic counseling by reliably identifying patients' psychosocial needs. The Genetic Psychosocial Risk Instrument (GPRI) is a validated genetic-specific screening tool designed to identify psychological risk factors that predict distress in patients having genetic testing. This questionnaire-based study investigated the perceived acceptability, feasibility, and usefulness of the GPRI in patients and clinicians in routine clinical genetic practice. From December 2018 to January 2019, 154 patients attending an Australian clinical genetic service were invited to complete a paper-based survey that included the GPRI. The GPRI was scored and provided to the clinician for use in the appointment. In February 2019, clinicians completed an anonymous online survey regarding acceptability, feasibility, and usefulness of the GPRI. Descriptive statistics, chi-squared, t tests, and regression analyses were used to analyze the patient data, and descriptive statistics were employed for clinician surveys. A total of 145 patients participated (94% response rate). The average GPRI score was 46.3 (95% CI 43.6-49.0) with 41% of patients meeting the 50-point threshold indicating high risk for psychological distress. The GPRI was highly acceptable to patients, regardless of their level of psychosocial risk. Fourteen clinicians participated (54% response rate): 85% found the GPRI not too time consuming, and 86% believed it improved patient care by identifying patient needs. All were willing to use the GPRI routinely. The use of the GPRI is highly acceptable to patients and clinicians in this setting, assisting in identifying patients at risk for distress, prompting clinicians to address concerns, provide psychosocial support, and consider ongoing referral. As 41% of patients' scores indicated a high risk of distress, the GPRI is an important tool for potentially enhancing overall patient outcomes.

How can Australia integrate routine genetic sequencing in oncology: a qualitative study through an implementation science lens.

PURPOSE: This study sought to determine genetics and oncology specialists' views of integrating BRCA1 and BRCA2 testing in epithelial ovarian and breast cancer into routine practice. METHODS: Qualitative interviews were designed using the Consolidated Framework for Implementation Research. Questions included experiences or views of the BRCA testing processes, implementation needs of oncology health professionals, perceived challenges, and future ideas for interventions to integrate genetic testing into oncology. RESULTS: Twenty-two participants were interviewed from twelve health organizations and four themes were identified: (1) embracing the shift to mainstream genetic testing, with the majority of participants viewing BRCA testing as clinically useful and routine use important for maintaining a patient centered process; (2) the need for communication networks and role delineation to integrate routine genetic testing; (3) factors that influence sustaining routine genetic testing, including ongoing training, resources and funding, real-world adaptation, system complexity, and champions; and (4) variation in system interventions for integrating routine genetic testing align to organizational context. CONCLUSION: Findings illustrate the need for integrating genetic testing into routine oncology, and that adaptation of interventions and processes is essential to sustain a feasible model. An understanding of individual and organizational implementation factors will help to prepare for future integration of routine genetic testing in other cancers.

Mainstreaming cancer genetics: A model integrating germline BRCA testing into routine ovarian cancer clinics.

OBJECTIVE: Owing to the rapid increase in clinical need, we aimed to implement and review the performance of a mainstreaming model of germline BRCA1/2 genetic testing in eligible women with high grade non-mucinous epithelial ovarian cancer via a Genetic Counselor embedded in the gynecology oncology clinic. METHODS: The model implemented involved a specialized referral form, weekly genetics-lead multidisciplinary review of referrals, and pre- and post-test genetic counseling provided by an embedded genetic counselor during chemotherapy chair time. Performance and outcomes were retrospectively audited over the following two consecutive one year periods, including survey data on medical specialist comfort with mainstreaming and the model. RESULTS: Sixty-four women underwent mainstreamed BRCA1/2 testing over the two year post-implementation period with a rate of detection of BRCA1/2 pathogenic variants of 17%. The referral rate for eligible women significantly increased to over 90% (p<0.001). The median time from referral to delivery of genetic testing results was less than five months, with >90% of patients receiving results during first line chemotherapy. Genetic counseling time decreased from 120 to 54min. Cancer specialists were comfortable with the model. CONCLUSIONS: The mainstreaming model proved effective, increasing uptake of genetic testing in eligible patients to over 90%; it was efficient for patients, genetic counselors and cancer specialists and acceptable to cancer specialists. It facilitated co-location of genetic and oncology service delivery but separation of clinical responsibility for genetic testing to a specialist genetics service, ensuring accurate and robust patient-centred care.

Personalising genetic counselling (POETIC) trial: Protocol for a hybrid type II effectiveness-implementation randomised clinical trial of a patient screening tool to improve patient empowerment after cancer genetic counselling.

BACKGROUND: Genetic counselling aims to identify, and address, patient needs while facilitating informed decision-making about genetic testing and promoting empowerment and adaptation to genetic information. Increasing demand for cancer genetic testing and genetic counsellor workforce capacity limitations may impact the quality of genetic counselling provided. The use of a validated genetic-specific screening tool, the Genetic Psychosocial Risk Instrument (GPRI), may facilitate patient-centred genetic counselling. The aim of this study is to assess the effectiveness and implementation of using the GPRI in improving patient outcomes after genetic counselling and testing for an inherited cancer predisposition. METHODS: The PersOnalising gEneTIc Counselling (POETIC) trial is a hybrid type 2 effectiveness-implementation trial using a randomised control trial to assess the effectiveness of the GPRI in improving patient empowerment (primary outcome), while also assessing implementation from the perspective of clinicians and the healthcare service. Patients referred for a cancer risk assessment to the conjoint clinical genetics service of two metropolitan hospitals in Victoria, Australia, who meet the eligibility criteria and consent to POETIC will be randomised to the usual care or intervention group. Those in the intervention group will complete the GPRI prior to their appointment with the screening results available for the clinicians' use during the appointment. Appointment audio recordings, clinician-reported information about the appointment, patient-reported outcome measures, and clinical data will be used to examine the effectiveness of using the GPRI. Appointment audio recordings, health economic information, and structured interviews will be used to examine the implementation of the GPRI. DISCUSSION: The POETIC trial takes a pragmatic approach by deploying the GPRI as an intervention in the routine clinical practice of a cancer-specific clinical genetics service that is staffed by a multidisciplinary team of genetics and oncology clinicians. Therefore, the effectiveness and implementation evidence generated from this real-world health service setting aims to optimise the relevance of the outcomes of this trial to the practice of genetic counselling while enhancing the operationalisation of the screening tool in routine practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry registration number 12621001582842p. Date of registration: 19th November 2021.

A mainstreaming oncogenomics model: improving the identification of Lynch syndrome.

Introduction: "Mainstreaming" is a proposed strategy to integrate genomic testing into oncology. The aim of this paper is to develop a mainstreaming oncogenomics model by identifying health system interventions and implementation strategies for mainstreaming Lynch syndrome genomic testing. Methods: A rigorous theoretical approach inclusive of conducting a systematic review and qualitative and quantitative studies was undertaken using the Consolidated Framework for Implementation Research. Theory-informed implementation data were mapped to the Genomic Medicine Integrative Research framework to generate potential strategies. Results: The systematic review identified a lack of theory-guided health system interventions and evaluation for Lynch syndrome and other mainstreaming programs. The qualitative study phase included 22 participants from 12 health organizations. The quantitative Lynch syndrome survey included 198 responses: 26% and 66% from genetic and oncology health professionals, respectively. Studies identified the relative advantage and clinical utility of mainstreaming to improve genetic test access and to streamline care, and adaptation of current processes was recognized for results delivery and follow-up. Barriers identified included funding, infrastructure and resources, and the need for process and role delineation. The interventions to overcome barriers were as follows: embedded mainstream genetic counselors, electronic medical record genetic test ordering, results tracking, and mainstreaming education resources. Implementation evidence was connected through the Genomic Medicine Integrative Research framework resulting in a mainstreaming oncogenomics model. Discussion: The proposed mainstreaming oncogenomics model acts as a complex intervention. It features an adaptable suite of implementation strategies to inform Lynch syndrome and other hereditary cancer service delivery. Implementation and evaluation of the model are required in future research.

Pilot study of an online training program to increase genetic literacy and communication skills in oncology healthcare professionals discussing BRCA1/2 genetic testing with breast and ovarian cancer patients.

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.

Stakeholders' views of integrating universal tumour screening and genetic testing for colorectal and endometrial cancer into routine oncology.

Mainstream genetic testing in routine oncology care requires implementation research to inform intervention design. In Australia, funding is available for oncology health professionals (OHP) to organise genetic testing (GT) for eligible colorectal and endometrial cancer patients as part of their routine care. To assess the health system ability to incorporate this practice change, we conducted an implementation survey using the Consolidated Framework for Implementation Research (CFIR). The online survey was available from April to September 2020 to OHP and genetic health professional (GHP). In total, 198 respondents attempted the survey, with 158 completed and 27 partial responses: 26% were GHP, 66% OHP and 8% pathologists. Of all responders, 50% were female, mainly practicing in public hospital settings (57%) in an urban location (80%) and with an 18-60 years plus age range. The majority of respondents saw the relative advantage of aligning GT to abnormal universal tumour screening (UTS) results, with 77% of GHP and 78% of OHP agreeing it would streamline care for patients. There was disagreement across healthcare professional groups about knowledge and self-efficacy, with 45% of GHP not viewing oncologists as 'feeling confident' to use genetic test results for treatment management decisions, while 62% of OHP felt confident in their ability. Both OHP and GHP's indicated embedding a genetic counsellor in oncology or having a genetics point of contact to support integrating of GT through UTS as favourable interventions. Implementation research findings allow for the design of targeted interventions and a model for GT integration into oncology.

Experiences and interpretations of BRCA1/2 testing among women affected by breast or ovarian cancer who received a negative result.

The aim of this study was to retrospectively describe the genetic testing motives and experiences of women with a previous breast and/or ovarian cancer diagnosis, who received negative BRCA1/2 results including variants of unknown significance and no pathogenic variant detected. One hundred and thirteen women (mean age 56.17 years) were recruited from a familial cancer centre in metropolitan Australia, an average 3.4 years after undergoing testing. Participants completed a self-report questionnaire focusing on the retrospective experience of and motives for undergoing BRCA1/2 testing. The study found that the primary motives for undergoing BRCA1/2 testing were (a) to know more about whether their cancer was hereditary, and (b) to have more certainty about the risk of their children developing cancer. In terms of perceptions of personal risk, 35% of women perceived that their risk of breast cancer to be the same or lower than the general population and 80% believed the negative test result to mean that a risk-conferring gene had not been detected. Yet, the average estimate of the likelihood that their cancer was hereditary was 48 out of a possible 100. Psychologically, women did not interpret the negative BRCA1/2 result as a positive outcome. Half were not relieved by the result and were as or more worried than before. Psychological morbidity was high with 17%, 100%, and 36% experiencing clinically significant depression, anxiety, and cancer-specific distress, respectively. Self-ratings of the likelihood that their cancer was hereditary were more closely associated with their personal family cancer histories than with measures of psychological distress. These results have implications for adherence to risk-reducing behaviours and quality of life. Given that these women are not routinely followed up in clinical practice, these findings highlight the importance of post-test genetic counselling and longer-term follow-up for women with negative BRCA1/2 results. Additional time and emotional support from genetic counsellors may help this group of women make sense of the meaning of their test result and adjust psychologically, particularly to uncertainty around the cause of their family history.

Vestibular schwannoma in a patient with neurofibromatosis type 1: clinical report and literature review.

We describe a young patient with typical neurofibromatosis type 1 on the basis of a mutation in the NF1 gene, who was diagnosed with a unilateral vestibular schwannoma caused by a somatic mutation in the NF2 gene. This combination has not been described before. This report highlights the requirement for ongoing surveillance regarding other manifestations of neurofibromatosis type 2 in such patients, as mosaicism cannot be ruled out. In addition to the NF1 mutation, the NF2 mutation should be considered in such cases if pre-implantation genetic diagnosis in undertaken.