UK consensus recommendations for clinical management of cancer risk for women with germline pathogenic variants in cancer predisposition genes: RAD51C, RAD51D, BRIP1 and PALB2.

Germline pathogenic variants (GPVs) in the cancer predisposition genes BRCA1, BRCA2, MLH1, MSH2, MSH6, BRIP1, PALB2, RAD51D and RAD51C are identified in approximately 15% of patients with ovarian cancer (OC). While there are clear guidelines around clinical management of cancer risk in patients with GPV in BRCA1, BRCA2, MLH1, MSH2 and MSH6, there are few guidelines on how to manage the more moderate OC risk in patients with GPV in BRIP1, PALB2, RAD51D and RAD51C, with clinical questions about appropriateness and timing of risk-reducing gynaecological surgery. Furthermore, while recognition of RAD51C and RAD51D as OC predisposition genes has been established for several years, an association with breast cancer (BC) has only more recently been described and clinical management of this risk has been unclear. With expansion of genetic testing of these genes to all patients with non-mucinous OC, new data on BC risk and improved estimates of OC risk, the UK Cancer Genetics Group and CanGene-CanVar project convened a 2-day meeting to reach a national consensus on clinical management of BRIP1, PALB2, RAD51D and RAD51C carriers in clinical practice. In this paper, we present a summary of the processes used to reach and agree on a consensus, as well as the key recommendations from the meeting.

A digital pathway for genetic testing in UK NHS patients with cancer: BRCA-DIRECT randomised study internal pilot.

BACKGROUND: Germline genetic testing affords multiple opportunities for women with breast cancer, however, current UK NHS models for delivery of germline genetic testing are clinician-intensive and only a minority of breast cancer cases access testing. METHODS: We designed a rapid, digital pathway, supported by a genetics specialist hotline, for delivery of germline testing of BRCA1/BRCA2/PALB2 (BRCA-testing), integrated into routine UK NHS breast cancer care. We piloted the pathway, as part of the larger BRCA-DIRECT study, in 130 unselected patients with breast cancer and gathered preliminary data from a randomised comparison of delivery of pretest information digitally (fully digital pathway) or via telephone consultation with a genetics professional (partially digital pathway). RESULTS: Uptake of genetic testing was 98.4%, with good satisfaction reported for both the fully and partially digital pathways. Similar outcomes were observed in both arms regarding patient knowledge score and anxiety, with <5% of patients contacting the genetics specialist hotline. All progression criteria established for continuation of the study were met. CONCLUSION: Pilot data indicate preliminary demonstration of feasibility and acceptability of a fully digital pathway for BRCA-testing and support proceeding to a full powered study for evaluation of non-inferiority of the fully digital pathway, detailed quantitative assessment of outcomes and operational economic analyses. TRIAL REGISTRATION NUMBER: ISRCTN87845055.

'A good decision is the one that feels right for me': Codesign with patients to inform theoretical underpinning of a decision aid website.

INTRODUCTION: Patient decision aids (PtDA) complement shared decision-making with healthcare professionals and improve decision quality. However, PtDA often lack theoretical underpinning. We are codesigning a PtDA to help people with increased genetic cancer risks manage choices. The aim of an innovative workshop described here was to engage with the people who will use the PtDA regarding the theoretical underpinning and logic model outlining our hypothesis of how the PtDA would lead to more informed decision-making. METHODS: Short presentations about psychological and behavioural theories by an expert were interspersed with facilitated, small-group discussions led by patients. Patients were asked what is important to them when they make health decisions, what theoretical constructs are most meaningful and how this should be applied to codesign of a PtDA. An artist created a visual summary. Notes from patient discussions and the artwork were analysed using reflexive thematic analysis. RESULTS: The overarching theme was: It's personal. Contextual factors important for decision-making were varied and changed over time. There was no one 'best fit' theory to target support needs in a PtDA, suggesting an inductive, flexible framework approach to programme theory would be most effective. The PtDA logic model was revised based on patient feedback. CONCLUSION: Meaningful codesign of PtDA including discussions about the theoretical mechanisms through which they support decision-making has the potential to lead to improved patient care through understanding the intricately personal nature of health decisions, and tailoring content and format for holistic care. PATIENT CONTRIBUTION: Patients with lived experience were involved in codesign and coproduction of this workshop and analysis as partners and coauthors. Patient discussions were the primary data source. Facilitators provided a semi-structured guide, but they did not influence the patient discussions or provide clinical advice. The premise of this workshop was to prioritise the importance of patient lived experience: to listen, learn, then reflect together to understand and propose ideas to improve patient care through codesign of a PtDA.

Breast cancer risk assessment for prescription of Menopausal Hormone Therapy in women who have a family history of breast cancer.

Background Menopausal Hormone Therapy (MHT) can alleviate menopausal symptoms but is associated with increased risk of breast cancer (BC). MHT prescription should be preceded by individualised risk/benefit evaluation; however, data outlining the impact of family history alongside different MHT therapeutic approaches are lacking. Aim To quantify the risks associated with MHT use in women with varying BC family histories of i) developing and ii) dying from BC. Design and setting An epidemiological modelling study (UK women). Method We used i) background risks of BC by age and family history, ii) relative risks for BC associated with MHT use, and iii) 10-year BC-specific net mortality rates to model the risk of developing and dying from BC between the ages of 50 and 80 in women with four different BC family history profiles: 'average', 'modest', 'intermediate', and 'strong'. Results For a woman of 'average' family history taking no MHT, the cumulative BC risk (age 50-80) is 9.8%, and the risk of dying from the BC is 1.7%. Five years' exposure to combined-cyclical MHT (age 50-55) increases these risks to 11.0% and 1.8%, respectively. For a woman with a 'strong' family history taking no MHT, the cumulative BC risk is 19.6%, and the risk of dying is 3.2%. With 5 years of MHT (age 50-55), this increases to 22.4% and 3.5%. Conclusion Both family history and MHT are associated with increased risk of BC. Estimates of the risks associated with MHT for women with different family histories can support decision-making around MHT prescription.

"Good practices" in pediatric clinical care for disorders/differences of sex development.

PURPOSE: To define, benchmark, and publicize elements of quality care (i.e., "good practices") for pediatric patients with disorders/differences of sex development (DSD). METHODS: Principles of quality care were identified by literature review; consensus exists for 11 good practices and adherence was evaluated through online survey of 21 North American clinical sites. RESULTS: Strong uptake was observed for many practices, particularly specialty participation (n ≥ 17 of 21 sites for most core specialties); point of contact (n = 18); expertise in gender dysphoria/dissatisfaction (n = 20); and DSD-specific continuing medical education (n = 18). Greater variability was apparent for frequency of peer support referrals (n = 12 universally practiced); standardized questionnaires for routine assessment of psychosocial adaptation (n = 13) and gender development (n = 10); consistently clarifying patient/family values in decision-making (n = 15); genital exam protocols that exclude trainee education as primary reason (n = 15); and internal patient-tracking efforts (n = 5-10 of 20 sites). CONCLUSION: This study employed a novel approach to designate DSD good practices and identified areas of consistency and variation in these DSD clinical practices. Good practice benchmarking facilitates quality assessment within and across sites, promotes continuous improvement, and empowers stakeholders in locating and delivering high quality care.