Breast cancer survivors face significant uncertainty after treatment because current follow-up methods, such as clinical review and imaging, often detect relapse only once disease is clinically evident.
Earlier detection could enable more timely intervention and improve outcomes, but existing blood biomarkers lack sufficient sensitivity and specificity.
This work aimed to evaluate whether personalised circulating tumour DNA (ctDNA) assays could detect relapse earlier and more accurately. The need is greatest for patients at higher risk of recurrence, including those with triple negative (TNBC) and hormone receptor positive breast cancer, where relapse may occur months or years after treatment.
Improving surveillance could expand treatment options, reduce disease burden, and provide reassurance to patients who remain disease-free.
In the Exploratory Breast Lead Interval Study (EBLIS), working with the US-based company Natera, 156 patients were followed for up to 12 years using personalised tumour-informed Signatera™ ctDNA assays.
Interim results showed ctDNA detection preceded relapse in 89% of cases, and final analysis confirmed high sensitivity (88.2%), with ctDNA identifying relapse up to three years earlier than standard methods (median lead time 10.5 months). Prognostic performance was particularly strong in TNBC.
These findings supported key regulatory milestones in the US, including FDA Breakthrough Device designation (2019) and Medicare coverage (2023).
This work demonstrates that ctDNA testing can transform post-treatment surveillance by enabling earlier, more personalised intervention and improving reassurance for patients with negative results. It has influenced clinical approaches to integrating molecular monitoring into follow-up pathways and supports ongoing ctDNA-guided treatment trials.
Earlier detection has the potential to reduce costs associated with advanced disease and improve efficiency through risk-stratified care. With sensitivity of 88.2% and detection up to three years earlier, this approach could deliver significant NHS savings and improved outcomes. The study also enabled global adoption of Signatera™, strengthening UK-led research and innovation in precision oncology.
This work supports the sickness to prevention shift detailed in the NHS 10 Year Health Plan for England.
Find out more
- Personalized detection of circulating tumor DNA antedates breast cancer metastatic recurrence Clin Cancer Res 25 (14): 4255–4263 (2019). DOI: https://doi.org/10.1158/1078-0432.CCR-18-3663
- Serial postoperative circulating tumor DNA assessment has strong prognostic value during long-term follow-up in patients with breast cancer. JCO Precis Oncol 8, e2300456 (2024).
DOI:10.1200/PO.23.00456 - Our publication from 2019 is cited on the Natera website as a pivotal paper for their technology (ref 2 of 3 cited): https://www.natera.com/oncology/signatera-advanced-cancer-detection/
- Other Natera publications that have resulted from this pivotal work:
https://www.natera.com/resource-library/natera-publications/signatera-publications/