Researchers have demonstrated that a streamlined genetic testing approach could identify more people with inherited breast cancer risk, while reducing the burden on NHS breast and genetic services.
The study, led by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, evaluated a genetic testing pathway called BRCA-DIRECT. The researchers successfully tested more than 3,500 patients from 14 diverse North London breast units, finding that 4.7% carry a potentially harmful inherited genetic profile linked to breast cancer.
Their findings, published in npj Breast Cancer, suggest that simplifying NHS eligibility criteria for testing could substantially increase the number of genetic mutations identified without immediately requiring every person diagnosed with breast cancer to undergo testing.
The study was funded by the Small Business Research Initiative (SBRI) Healthcare, which partners with NHS England’s Cancer Programme to identify and implement pioneering inventions into front-line clinical settings. The BRCA-DIRECT pathway has been commissioned by NHS England for national delivery of ‘Direct-to-Patient’ (DTP) genetic testing, which will be led by the North Thames Genomic Laboratory Hub and commence by April 2027.
Some breast cancers are caused or influenced by inherited mutations in so-called susceptibility genes, which include high impact genes such as BRCA1, BRCA2 and PALB2. As these mutations increase the risk of developing the disease, identifying them post-diagnosis can greatly assist healthcare professionals in making decisions about a patient’s treatment, based on their future cancer risk. It can also allow relatives to find out whether they have inherited the same mutation and may benefit from additional diagnostic screening or other risk-reducing measures.
BRCA-DIRECT is a high-throughput, clinician-light and expert genetics-supported pathway designed to remove the repetitive, generic, time-insensitive and low-value steps from the patients’ pathway. It was co-designed and developed by a team across The Institute of Cancer Research (ICR) and The Royal Marsden, led by Professor Clare Turnbull, as well as support from patients, clinicians and wider healthcare professionals.
In the study, instead of routine in-person appointments and blood tests, patients were able to complete consent forms and collect saliva samples at home, returning them via post to The Royal Marsden for analysis. Across the 3,515 newly diagnosed breast cancer patients who completed genetic testing, 166 potentially harmful inherited genetic changes were identified across the seven breast cancer susceptibility genes tested for in the UK (BRCA1, BRCA2, PALB2, ATM, CHEK2, RAD51C and RAD51D) – equivalent to a detection rate of 4.7%.
The team then used these results to investigate how many mutations would have been identified applying BRCA-DIRECT under current NHS criteria. They found only 20.6% of patients in Professor Turnbull’s study would have been offered genetic testing, despite 49.2% of them carrying potentially harmful genetic mutations in the three high-susceptibility genes.
The team therefore developed a set of proposed ‘ultra-simple’ eligibility criteria, designed to be easier for breast cancer healthcare professionals to apply when assessing detailed family histories. Applying these criteria would make testing available to 49.7% of breast cancer patients, which would increase BRCA1, BRCA2 and PALB2 detection to 81.1%.
The study found that expanding access to testing through BRCA-DIRECT was feasible to both patients and healthcare professionals. Overall, 86 per cent of patients referred to the programme completed the at-home testing offered, reporting high satisfaction and low regret about their decision to undergo genetic testing.
Following implementation, 35 breast and genetics HCPs were surveyed. Of the breast healthcare professionals, 88.9 per cent reported offering testing to most patients and all stated that they wanted to continue with and recommend testing via the BRCA-DIRECT pathway. Of the genetics healthcare professionals, 66.7 per cent reportedly observed a decrease in referrals received. The team also found that breast cancer clinicians generally favoured simpler and broader eligibility criteria, while genetics professionals were more cautious about expanding testing because of the potential implications for NHS resources.
- Torr B, Mansour L, Fierheller CT, et al. Routine germline genetic testing in 3552 unselected NHS breast cancer patients: evidence informing testing criteria and implementation of a 'BRCA-DIRECT' mainstreaming pathway. NPJ Breast Cancer. Published online July 9, 2026. doi:10.1038/s41523-026-01000-4