Researchers at The Institute of Cancer Research, London, have developed an ultra-sensitive blood test that can predict breast cancer recurrence months or even years before tumors become detectable on conventional scans. The breakthrough, presented at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, represents a significant advance in early cancer detection technology.
Revolutionary Detection Capabilities
The new liquid biopsy test demonstrated remarkable accuracy in a five-year trial involving 78 patients with different types of early breast cancer. The test successfully identified all 11 patients who eventually relapsed, with an average lead time of 15 months before clinical symptoms appeared. The longest prediction window extended to 41 months, providing unprecedented early warning of cancer recurrence.
"Breast cancer cells can remain in the body after surgery and other treatments but there can be so few of these cells that they are undetectable on follow-up scans," explained Dr. Isaac Garcia-Murillas, the study's lead author at the ICR. "These cells can cause breast cancer patients to relapse many years after their initial treatment."
Enhanced Sensitivity Through Whole Genome Sequencing
The test's superior performance stems from its use of whole genome sequencing (WGS) technology, which analyzes up to 1,800 mutations in a patient's tumor DNA. This approach represents a significant improvement over conventional tests that typically use whole exome sequencing to examine only 16-50 mutations.
The enhanced sensitivity proved crucial for detecting circulating tumor DNA (ctDNA) - tiny fragments of cancer DNA released into the bloodstream by cancer cells. Among the 78 patients studied, the test correctly identified high recurrence risk in all patients who later relapsed, while producing no false negatives among the 60 women who remained cancer-free throughout the follow-up period.
Clinical Trial Results and Patient Outcomes
The study analyzed blood samples from patients with various breast cancer subtypes: 23 with triple-negative breast cancer, 35 with HER2+ breast cancer, 18 with hormone receptor-positive breast cancer, and two with unknown subtypes. Blood samples were collected at multiple time points, including diagnosis, after chemotherapy cycles, following surgery, and during regular follow-up visits.
Detection of ctDNA at any point after surgery or during follow-up was associated with high risk of future relapse and poorer overall survival. The median survival for patients with detectable ctDNA was 62 months, while survival had not been reached for patients without detectable ctDNA by the study's end.
Implications for Treatment Strategy
Professor Kristian Helin, Chief Executive of the ICR, emphasized the clinical significance of early detection: "Breast cancer is much easier to treat before it spreads to other parts of the body, so it is vital to be able to detect signs of recurrence as early as possible to give people the best chance of survival."
The findings could enable a new treatment paradigm where intervention begins much earlier, potentially before cancer becomes incurable advanced disease. Dr. Simon Vincent, director of research at Breast Cancer Now, which helped fund the trial, noted that "catching breast cancer recurrence earlier means treatment is much more likely to destroy the cancer and stop it spreading to other parts of the body, at which point it becomes incurable."
Future Research Directions
While the results are promising, researchers acknowledge that further studies are needed to determine how molecular residual disease detection could guide therapy decisions. Professor Nicholas Turner, Professor of Molecular Oncology at the ICR, noted that "further research and testing are needed before we can demonstrate whether detecting molecular residual disease could guide therapy in the future."
The ongoing TRAK-ER trial at The Royal Marsden is already investigating whether relapse in patients with residual disease could be prevented by altering their treatment based on molecular test results.
Global Impact Potential
With more than 2 million women diagnosed with breast cancer annually worldwide, and approximately 11,000 deaths from secondary breast cancer each year in the UK alone, this technology could have significant global health implications. The test was developed in collaboration with Personalis, Inc., makers of the NeXT Personal test, suggesting potential for broader clinical implementation.
Dr. Richard Chen, Chief Medical Officer at Personalis, expressed enthusiasm about the collaboration: "The study shows the importance and promise of using an ultra-sensitive MRD test like NeXT Personal to detect the earliest traces of breast cancer recurrence, and more optimally guide management of breast cancer patients."
