Novel ctDNA Liquid Biopsy May Help Predict Breast Cancer Recurrence Years Before Relapse

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A novel ultrasensitive liquid biopsy may be predictive of breast cancer recurrence up to years prior to relapse in high-risk patients with early breast cancer, according to recent findings presented by Garcia-Murillas et al at the 2024 ASCO Annual Meeting (Abstract 1010).


Circulating tumor DNA (ctDNA) is released into the bloodstream by cancer cells and can be used to detect molecular residual disease following breast cancer therapy.

“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. These cells can cause [patients with] breast cancer to relapse many years after their initial treatment. Ultra-sensitive blood tests could offer a better approach for the long-term monitoring of patients whose cancer is at high risk of returning,” explained lead study author Isaac Garcia-Murillas, PhD, a staff scientist in the Molecular Oncology Group at The Institute of Cancer Research in London.

Although previous studies have shown that ctDNA liquid biopsies may identify relapse long before it can be observed on a scan, most tests use a technique called whole-exome sequencing that focuses on exons directly related to disease.

Study Methods and Results

In this study, researchers used blood samples from the ChemoNEAR sample collection study to detect the presence of ctDNA in 78 patients with early breast cancer—35 of whom had HER2-positive breast cancer, 23 of whom had triple-negative breast cancer, 18 of whom had hormone receptor–positive breast cancer, and 2 of whom had an unknown breast cancer subtype.

The researchers noted that the samples were collected from the patients at diagnosis prior to treatment initiation, following the second cycle of chemotherapy, following surgery, and every 3 months during follow-up for the first year. After that, the samples were collected every 6 months for the next 5 years.

The novel approach involved whole-genome sequencing and enabled the researchers to identify up to 1,800 mutations—which the investigator said was far more sensitive and included a larger number of cancer-related changes that could occur in a patient’s DNA.

The researchers discovered that the detection of ctDNA at any point following surgery or during follow-up was associated with a high risk of future relapse and poorer overall survival. Additionally, molecular residual disease was detected in all 11 patients who later relapsed. The median lead time to clinical relapse was 15 months, representing an increase of over 3 months compared with current tests in all types of breast cancer. The longest lead time to clinical relapse was 41 months.

The researchers reported that 0% (n = 0/60) of the patients in whom ctDNA remained undetected relapsed throughout follow-up, and three of the patients had detectable ctDNA in the follow-up period but had not relapsed by the end of the study. The median survival for patients with detectable or undetectable ctDNA was 62 months and not reached, respectively.


“This proof-of-principle retrospective study lays the groundwork for better posttreatment monitoring and potentially life-extending treatment in patients. [T]his approach goes one step further and uses whole-genome sequencing to … uniquely identify recurrence of the patient’s cancer from a blood sample. A more sensitive test is very important for this group of [patients with] early breast cancer, as they tend to have a very low amount of cancer DNA in their blood,” highlighted Dr. Garcia-Murillas.

“Testing a patient’s blood for ctDNA will allow clinicians to diagnose the return of cancer at the very earliest stage. However, further research and testing are needed before we can demonstrate whether detecting molecular residual disease could guide therapy in the future,” emphasized co–study author Nicholas Turner, PhD, Professor of Molecular Oncology at The Institute of Cancer Research and a consultant medical oncologist at The Royal Marsden National Health Service Foundation Trust. “The ongoing TRAK-ER trial at The Royal Marsden, for example, is using a different molecular test to identify circulating tumor DNA and predict relapse in [patients with estrogen receptor–positive] breast cancer. This trial is looking at whether relapse in patients with residual disease could be prevented by altering their treatment,” he added.

By determining which patients may be most likely to relapse, the researchers hope their results will pave the way for a new strategy to treat recurrent breast cancer in which therapy can be administered much earlier—without waiting for the cancer to advance to an incurable stage.

“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 of the disease as early as possible to give [patients] the best chance of survival,” stated Kristian Helin, MSc, PhD, Chief Executive of The Institute of Cancer Research. “It is very exciting to see advances in technology that can detect cancer cells and DNA with greater sensitivity to pick up residual disease or detect the early signs of breast cancer recurrence while a cure is still possible. These approaches are having a transformative effect on cancer diagnosis. They will help us exploit our knowledge of cancer risk to develop new strategies for targeted screening and detection,” he suggested.

“Early detection is one of our greatest weapons against breast cancer, and these initial findings, which suggest new tests could be able to detect signs of breast cancer recurrence over 1 year before symptoms emerge, are incredibly exciting. While this research is still in its early stages, catching breast cancer recurrence earlier means treatment is much more likely to destroy the cancer and stop it [from] spreading to other parts of the body, at which point it becomes incurable. [B]reakthroughs like these are urgently needed so that we can stop [patients from] losing their lives to this devastating disease,” concluded Simon Vincent, PhD, Director of Research, Support, and Influencing at Breast Cancer Now.

Disclosure: The research in this study was funded by Personalis and Breast Cancer Now. For full disclosures of the study authors, visit

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