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Background: Genetic testing to identify germline high-risk pathogenic variants in breast cancer susceptibility genes is increasingly part of the breast cancer diagnostic pathway. Novel patient-centred pathways may offer opportunity to expand capacity and reduce turnaround time., Methods: We recruited 1140 women with unselected breast cancer to undergo germline genetic testing through the BRCA-DIRECT pathway (which includes a digital platform, postal saliva sampling and a genetic counsellor telephone helpline). Ahead of consenting to the test, participants were randomised to receive information about genetic testing digitally (569/1140, 49.9%) or via a pre-test genetic counselling consultation (571/1140, 50.1%)., Results: 1001 (87.8%) participants progressed to receive their pre-test information and consented to testing. The primary outcome, uptake of genetic testing, was higher amongst participants randomised to receive digital information compared with those randomised to a pre-test genetic counselling consultation (90.8% (95% CI: 88.5% to 93.1%) vs 84.7% (95% CI: 81.8% to 87.6%), p = 0.002, adjusted for participant age and site). Non-inferiority was observed in relation to patient knowledge, anxiety, and satisfaction., Conclusions: Findings demonstrate that standardised, digital information offers a non-inferior alternative to conventional genetic counselling, and an end-to-end patient-centred, digital pathway (supported by genetic counselling hotline) could feasibly be implemented into breast oncology settings., Clinical Trial Registration: The study is registered with, and protocol available on, ClinicalTrials.gov (NCT04842799)., (© 2024. The Author(s).)

Background: Menopausal hormone therapy (MHT) can alleviate menopausal symptoms but has been associated with an increased risk of breast cancer. 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 breast cancer family histories of developing and dying from breast cancer., Design and Setting: An epidemiological modelling study for women in England using the BOADICEA breast cancer prediction model and data relating to MHT use and breast cancer risk taken from research by the Collaborative Group on Hormonal Factors in Breast Cancer., Method: The risk of developing and dying from breast cancer between the ages of 50 and 80 years was modelled in women with four different breast cancer family history profiles: 'average', 'modest', 'intermediate', and 'strong' by using 1) background risks of breast cancer by age and family history, 2) relative risks for breast cancer associated with MHT use, and 3) 10-year breast cancer-specific net mortality rates. This study modelled use of combined oestrogen-progestogen MHT (cyclical or continuous) and oestrogen-only MHT., Results: For a woman of 'average' family history taking no MHT, the cumulative breast cancer risk (age 50-80 years) is 9.8%, and the risk of dying from the breast cancer is 1.7%. In this model, 5 years' exposure to combined-cyclical MHT (age 50-55 years) was calculated to increase these risks to 11.0% and 1.8%, respectively. For a woman with a 'strong' family history taking no MHT, the cumulative breast cancer risk is 19.6% (age 50-80 years), and the risk of dying from the breast cancer is 3.2%. With 5 years' exposure to MHT (age 50-55 years), this model showed that these risks increase to 22.4% and 3.5%, respectively., Conclusion: In this model, both family history and MHT are associated with increased risk of breast cancer. Estimates of the risks of breast cancer associated with MHT for women with different family histories can be used to support decision making around MHT prescription for women experiencing menopausal symptoms., (© The Authors.)

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 R AD51D 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., Competing Interests: Competing interests: HH received honoraria from AstraZeneca for advisory roles. CT received honoraria from AstraZeneca and Roche for advisory roles, which were donated in full to charity (https://tukongote.com/, registration number 11511580, charity number 1186151). RM declares research funding from Barts & the London Charity, Rosetrees Trust, GSK, Eve Appeal, CRUK and Yorkshire Cancer Research outside this work; and honorarium for advisory board membership from AstraZeneca/MSD/GSK/EGL. DME was in receipt of research funding from AstraZeneca. ANR had prior consultancy arrangements with Abcodia and Everything Genetic. ACA was listed as a creator of BOADICEA, which was licensed by Cambridge Enterprise for commercial purposes., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)