“Left in limbo”: Exploring how patients with colorectal cancer interpret and respond to a suspected Lynch syndrome diagnosis

Background A diagnosis of suspected Lynch syndrome (SLS) is given when a tumour displays characteristics consistent with Lynch syndrome (LS), but no germline pathogenic variant is identified. This inconclusive diagnosis results in uncertainty around appropriate cancer risk management. This qualitative study explored how patients with CRC interpret and respond to an SLS diagnosis. Methods Semi-structured telephone interviews were conducted with 15 patients with CRC who received an SLS diagnosis, recruited from cancer genetics services across Australia. Interviews were transcribed verbatim and analysed using thematic analysis. Participant responses were compared with appointment summary letters from cancer genetics services. Results Participants’ interpretations of genetic test results were found to vary widely. While this variation often aligned with variation in interpretations by cancer genetics services, participants also had difficulties with the complexity and recall of genetic test results. Participants had a range of psychological responses to the uncertainty that their results presented, from relief to disappointment and doubt. Cancer risk perceptions also varied widely, with participants’ interpretations of their genetic test results just one of several influencing factors. Despite this variability, almost all participants adhered to cancer risk management advice, although different participants received different advice. All participants also communicated any cancer risk management advice to first-degree relatives, motivated by protecting them, but information communicated was not always consistent with advice received. Conclusions Our study findings highlight the variability in patients’ interpretations of their diagnosis, cancer risk management and family communication when a diagnosis of SLS is received, and provide novel insights into how healthcare professionals can better support patients with SLS.

Results from London Regional Clinical Genetics services over a 5-year period on germline TP53 testing in women diagnosed with breast cancer at <30 years

BackgroundThe most common cancer diagnosed in germline TP53 pathogenic variant (PV) carriers is premenopausal breast cancer. An increased rate of breast tumour HER2 positivity has been reported in this group. Screening for breast/other cancers is recommended in PV carriers.Objectives1. To assess the frequency of germline TP53 PVs reported diagnostically in women with breast cancer at <30 years of age.2. To evaluate the impact of personal/family history and HER2 status on the likelihood of germline TP53 pathogenic/likely pathogenic variant (PV/LPV) identification.MethodsGenetic test results from patients undergoing diagnostic germline TP53 tests between 2012 and 2017 in the four London Regional Clinical Genetics Services were reviewed. Clinical/pathology data and family history were extracted from genetics files for women diagnosed with breast cancer at <30 years.ResultsThe overall germline TP53 PV/LPV variant detection rate was 9/270=3.3% in all women diagnosed with breast cancer at <30 years and 2/171=1.2% in those with no second/subsequent cancer diagnosis or family history of TP53-spectrum cancers. Breast cancers were significantly more likely to be HER2-positive in TP53 PV/LPV carriers than in non-carriers (p=0.00006).ConclusionsGermline TP53 PVs/LPVs are uncommon among women diagnosed with breast cancer aged <30 years without other relevant personal or family cancer history but have an important clinical impact when identified.

Measuring physician practice, preparedness and preferences for genomic medicine: a national survey

ObjectiveEven as genomic medicine is implemented globally, there remains a lack of rigorous, national assessments of physicians’ current genomic practice and continuing genomics education needs. The aim of this study was to address this gap.DesignA cross-sectional survey, informed by qualitative data and behaviour change theory, to assess the current landscape of Australian physicians’ genomic medicine practice, perceptions of proximity and individual preparedness, and preferred models of practice and continuing education. The survey was advertised nationally through 10 medical colleges, 24 societies, 62 hospitals, social media, professional networks and snowballing.Results409 medical specialists across Australia responded, representing 30 specialties (majority paediatricians, 20%), from mainly public hospitals (70%) in metropolitan areas (75%). Half (53%) had contacted their local genetics services and half (54%) had ordered or referred for a gene panel or exome/genome sequencing test in the last year. Two-thirds (67%) think genomics will soon impact their practice, with a significant preference for models that involved genetics services (p<0.0001). Currently, respondents mainly perform tasks associated with pretest family history taking and counselling, but more respondents expect to perform tasks at all stages of testing in the future, including tasks related to the test itself, and reporting results. While one-third (34%) recently completed education in genomics, only a quarter (25%) felt prepared to practise. Specialists would like (more) education, particularly on genomic technologies and clinical utility, and prefer this to be through varied educational strategies.ConclusionsThis survey provides data from a breadth of physician specialties that can inform models of genetic service delivery and genomics education. The findings support education providers designing and delivering education that best meet learner needs to build a competent, genomic-literate workforce. Further analyses are underway to characterise early adopters of genomic medicine to inform strategies to increase engagement.

OP0079 LIMB GIRDLE MUSCULAR DYSTROPHY TYPE 2B - A RARE MYOSITIS MIMIC

Background:Proximal muscle weakness with associated raised creatine kinase (CK) commonly leads to referral to Rheumatology for the investigation of Idiopathic Inflammatory Myopathy (IIM). Some genetic myopathies can have a similar presentation with investigations that suggest inflammatory disease, leading to difficulty with accurate diagnosis (Amato & Brown, 2011; Harlan & Mammen, 2019).Objectives:To describe the case of a patient with Limb Girdle Muscular Dystrophy Type 2B (LGMD2B), whose initial presentation mimicked an inflammatory myopathy.Methods:Case report.Results:A 43-year-old patient was reviewed by Rheumatology due to proximal muscle weakness with a raised CK. Muscle biopsy was suggestive of inflammatory myopathy. Therefore, he was started on treatment with corticosteroids. Corticosteroid treatment resulted in no improvement in his weakness or CK. His diagnosis was reviewed, and he was referred to the Neurology and Genetics services. Following molecular genetic analysis, a diagnosis of Limb Girdle Muscular Dystrophy Type 2B was made.Conclusion:Muscle biopsies can suggest an inflammatory aetiology in some genetic myopathies (Amato & Brown, 2011; Harlan & Mammen, 2019). If a patient with suspected IIM presents with atypical features, or they do not respond as expected to treatment, then consider a genetic myopathy such as LGMD2B as a cause and involve the Neurology and Genetics services in the case.References:[1]Amato, A. A., & Brown, R. H., Jr. (2011). Dysferlinopathies. Handb Clin Neurol, 101, 111-118. https://doi.org/10.1016/b978-0-08-045031-5.00007-4[2]Harlan, M & Mammen A. L (2019). Myositis Mimics: The Differential Diagnosis of Myositis. In: R. Aggarwal and C. V. Oddis (Eds.) Managing Myositis (pp. 209-223). Springer, Cham.Disclosure of Interests:None declared

“This is my boy’s health! Talk straight to me!” perspectives on accessible and culturally safe care among Aboriginal and Torres Strait Islander patients of clinical genetics services

Background Aboriginal and Torres Strait Islander people do not enjoy equal access to specialist health services that adequately meet their needs. Clinical genetics services are at the vanguard of realising the health benefits of genomic medicine. As the field continues to expand in clinical utility and implementation, it is critical that Aboriginal and Torres Strait Islander people are able to participate and benefit equally to avoid further widening of the existing health gap. This is the first study to explore barriers to accessing clinical genetics services among Aboriginal and Torres Strait Islander people, which has been acknowledged as a key strategic priority in Australian genomic health policy. Methods A participatory design process engaged a majority-Aboriginal Project Reference Group and Aboriginal End-User Group. 63 semi-structured interviews were conducted with Aboriginal and/or Torres Strait Islander people who had accessed the government-funded clinical genetics service in Western Australia, Queensland or the Northern Territory between 2014 and 2018. The sample included patients, parents and carers. Participants were asked to recount their ‘patient journey’, from referral through to post-appointment and reflect on their perceptions of genetics and its implications for the health of themselves and their families. Analysis tracked chronological service engagement, followed by an inductive thematic approach. Results Barriers to access and engagement were present at each stage of the patient journey. These included challenges in obtaining a referral, long waiting periods, limited genetic literacy, absence of Aboriginal support services, communication challenges and lack of adequate psychosocial support and follow-up after attendance. Participants’ overall experiences of attending a genetic health service were varied, with positive perceptions tied closely to a diagnosis being achieved. The experience of (and expectation for) recognition of cultural identity and provision of culturally safe care was low among participants. Unaddressed concerns continued to cause significant distress in some people years after their appointment took place. Conclusions There is significant scope for improving the care provided to Aboriginal and Torres Strait Islander people at clinical genetics services. Immediate attention to minimising logistical barriers, developing relationships with Aboriginal Community Controlled Health Services and providing practical and specific cultural safety training for practitioners is required at the service-level. Our findings strongly support the development of guidelines or policies recognising the collective cultural needs of Aboriginal and Torres Strait Islander people in relation to genomic health care.