Summary: A new blood test can predict the recurrence of breast cancer in high-risk patients by detecting cancer DNA months or years before relapse.


  1. Researchers from The Institute of Cancer Research, London, used an ultra-sensitive liquid biopsy to detect tiny amounts of cancer DNA, identifying molecular residual disease and predicting relapse.
  2. The whole genome sequencing (WGS) approach in the study identified up to 1,800 mutations, providing a more sensitive and comprehensive detection method compared to whole exome sequencing (WES).
  3. The detection of ctDNA at any point after treatment was associated with a high risk of future relapse, allowing for earlier intervention and potentially improving patient outcomes by starting treatment before the cancer becomes advanced.

A new type of blood test can predict the recurrence of breast cancer in high-risk patients, months or even years before they relapse, research has shown.

A team from The Institute of Cancer Research, London, used an ultra-sensitive liquid biopsy to detect the presence of tiny amounts of cancer DNA left in the body following treatment for early breast cancer.

The findings, presented at the American Society of Clinical Oncology (ASCO) annual meeting involved analysing blood samples from the ChemoNEAR sample collection study for circulating tumour DNA (ctDNA) that is released into the bloodstream by cancer cells.

Liquid Biopsy ctDNA Test 

The researchers, based at the Breast Cancer Now Toby Robins Research Centre at The Institute of Cancer Research (ICR), were able to identify all patients from the study who later went on to relapse by detecting very low levels of cancer found in the blood – known as molecular residual disease.

“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,” says Nicholas Turner, Professor of Molecular Oncology at the ICR, and Consultant Medical Oncologist at The Royal Marsden NHS Foundation Trust. “The ongoing TRAK-ER trial at The Royal Marsden, for example, is using a different molecular test to identify circulating tumour DNA and predict relapse in ER positive breast cancer patients. This trial is looking at whether relapse in patients with residual disease could be prevented by altering their treatment.”

Treating Recurrent Breast Cancer

By helping to spot the patients most likely to relapse, the ICR scientists hope the results will pave the way for a new strategy for treating recurrent breast cancer where treatment can be started much earlier, without waiting for incurable, advanced disease to develop and show up on a scan.

Although previous studies have shown that ctDNA blood tests can identify relapse long before it can be seen on a scan, most tests use a technique called whole exome sequencing (WES) which look for between 16 and 50 mutations, depending on the test. WES focuses on the exons—the protein-coding regions of genes—which are directly related to diseases.

Breast Cancer Study

However, the approach in this study, which was funded by the U.S.-based company Personalis, Inc.—the makers of the NeXT Personal test—and the charity Breast Cancer Now, involves sequencing the entire genome, known as whole genome sequencing (WGS). This enabled researchers to identify up to 1,800 mutations which is much more sensitive and includes a larger number of cancer-related changes that could occur in a patient’s DNA.

Blood samples from 78 patients with different types of early breast cancer (23 with triple negative breast cancer, 35 with HER2+ breast cancer, 18 with hormone receptor+ breast cancer and two with an unknown subtype) were screened for ctDNA.

The samples were collected from the women at diagnosis before their therapy, after the second cycle of chemotherapy, following their surgery and every three months during follow-up for the first year. After that, samples were collected every six months for the next five years.

The results showed that detection of ctDNA at any point after surgery or during the follow-up period was associated with a high risk of future relapse and poorer overall survival.

Molecular residual disease was detected in all 11 patients who relapsed. The median lead time to clinical relapse in this group of patients was 15 months, an increase of over three months, compared with other ctDNA tests in all types of breast cancer. The longest lead time to clinical relapse was 41 months.

None of the 60 women in whom ctDNA remained undetected, relapsed throughout the follow-up period. Three patients had ctDNA detected in follow-up but had not relapsed by the end of the study – the researchers didn’t have samples to analyse beyond the study follow-up period. Four patients did not have post-baseline samples, so their results could not be followed up. Median survival for ctDNA detected patients was 62 months and not reached for the patients in whom ctDNA was undetected.

“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 breast cancer patients 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,” says Isaac Garcia-Murillas, PhD, staff scientist in the Molecular Oncology Group at The Institute of Cancer Research, London. “Most personalized liquid biopsies currently use whole exome sequencing to identify mutations. But this approach goes one step further and uses whole genome sequencing to identify up to 1,800 mutations in a patient’s tumor DNA that could uniquely identify the recurrence of the patient’s cancer from a blood sample. A more sensitive test is very important for this group of early breast cancer patients as they tend to have a very low amount of cancer DNA in their blood.”