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Ultra-Sensitive Blood Test Predicts Breast Cancer Recurrence Months or Even Years before Relapse

By LabMedica International staff writers
Posted on 07 Jun 2024
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Image: The ultra-sensitive blood test detects tiny amounts of cancer DNA left in the body after treatment for early breast cancer (Photo courtesy of ICR)
Image: The ultra-sensitive blood test detects tiny amounts of cancer DNA left in the body after treatment for early breast cancer (Photo courtesy of ICR)

Breast cancer cells can linger in the body after surgery and other treatments, sometimes in such low quantities that follow-up scans fail to detect them. These cells can cause a recurrence of breast cancer years after the initial treatment. Detecting breast cancer before it metastasizes is crucial for effective treatment and improving survival rates. Now, a new type of blood test can predict breast cancer recurrence in high-risk patients months or even years before relapse occurs.

A research team from The Institute of Cancer Research (London, UK) utilized an ultra-sensitive liquid biopsy to detect tiny amounts of cancer DNA remaining in the body after treatment for early breast cancer. The study involved analyzing blood samples for circulating tumor DNA (ctDNA) released into the bloodstream by cancer cells. While previous research has shown that ctDNA blood tests can identify relapse long before it appears on a scan, most of these tests use whole exome sequencing (WES), which examines 16 to 50 mutations depending on the test. WES focuses on the exons, the protein-coding regions of genes directly related to diseases. However, this study used whole genome sequencing (WGS), allowing researchers to identify up to 1,800 mutations, making it more sensitive and inclusive of a larger number of cancer-related changes 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-positive breast cancer, and two with an unknown subtype) were screened for ctDNA. The samples were collected at diagnosis before therapy, after the second cycle of chemotherapy, following surgery, and every three months during the first year of follow-up. Subsequently, samples were taken every six months for the next five years. The results showed that detecting ctDNA at any point after surgery or during follow-up was linked to 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 was 15 months, an increase of over three months compared to other ctDNA tests for 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 during the follow-up period. Three patients had ctDNA detected during follow-up but had not relapsed by the end of the study due to the lack of samples beyond the follow-up period. Four patients did not have post-baseline samples, so their results could not be followed up. The median survival for patients with detected ctDNA was 62 months, whereas it was not reached for those without detected ctDNA. By identifying patients most likely to relapse, researchers hope these findings will lead to a new strategy for treating recurrent breast cancer, enabling earlier treatment without waiting for advanced, incurable disease to manifest on a scan. 

“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 recurrence of the patient’s cancer from a blood sample,” said Dr. Isaac Garcia-Murillas, Staff Scientist in the Molecular Oncology Group at The Institute of Cancer Research. “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. This proof-of-principle retrospective study lays the groundwork for better post-treatment monitoring and potentially life-extending treatment in patients.”

Related Links:
The Institute of Cancer Research

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