New results from the PLASMAMATCH trial suggest that a blood test known as a ‘liquid biopsy’ could reveal much earlier whether treatment for metastatic breast cancer is effective.
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Professor Nick Turner and his team measured tiny fragments of cancer DNA, called circulating tumour DNA (ctDNA), in the blood of people living with metastatic breast cancer.
They found that people with low ctDNA levels at the start responded better to treatment. And that people whose ctDNA levels became undetectable after 4 weeks of treatment were more likely to respond well.
These findings add to over a decade of pioneering research into the use of liquid biopsies from our scientists at the Breast Cancer Now Toby Robins Research Centre at the Institute of Cancer Research, London.
A window into the tumour
Breast cancers release DNA into the blood. This circulating tumour DNA (ctDNA) is a very useful tool to track changes in breast cancer cells. That’s because it carries the same genetic changes as the cancer itself, so it offers a real-time view of how the cancer is behaving.
In this study, researchers analysed blood samples from 167 people with advanced breast cancer. Based on their type of cancer and specific gene changes, the participants were divided into 5 groups:
- People with an ESR1, HER2, AKT1, AKT or PTEN gene change (A-D)
- People with triple negative breast cancer and no gene changes (E)
People in group A-D received targeted treatments that matched their gene change. People in group E, who lacked these specific gene changes, received a combination of olarparib and ceralasertib.
The researchers took blood samples before treatment began and around 4 weeks later, just before their second treatment cycle. By comparing ctDNA levels at these 2 time points, the team hoped to understand whether early changes in ctDNA could reveal who was more likely to benefit from certain treatments.
Early clues that treatment is working
Nick and his team found that people with low ctDNA levels at the start responded better to treatment. This suggests that breast cancers that release higher levels of ctDNA might be more resistant to targeted therapies.
The researchers also showed that people whose ctDNA levels dropped to undetectable levels after 4 weeks were much more likely to respond well to treatment. And they tended to have longer periods before their cancer progressed.
For example, for people in group A-D, undetectable ctDNA levels at 4 weeks predicted a 46% response rate, compared with 8% in those whose ctDNA remained detectable. And it was linked to treatment working for around 10.6 months, compared with 3.5 months when ctDNA was still detectable.
For people in group E, those whose ctDNA levels became undetectable after four weeks had an 86% response rate, compared with just 11%. And it was linked with treatment working for 12 months, compared to 4.3.
Most of these people also didn’t have BRCA gene changes, suggesting this blood test could help identify who may respond to PARP inhibitors, even without these gene changes.
Our study shows that a simple blood test could give us an early and reliable indication of whether treatment is working for people with metastatic breast cancer. By tracking changes in tumour DNA in the blood just a few weeks into treatment, we can begin to identify who is likely to benefit and who may need a different approach sooner. This has the potential to make treatment decisions faster, more personalised and ultimately more effective for people living with metastatic breast cancer.
Professor Nick Turner
Towards faster, more personalised treatment decisions
These results build on earlier findings from 2020, which showed that liquid biopsies can accurately detect the genetic changes driving someone’s cancer and help match them to targeted treatments.
The researchers now hope to validate their findings in larger studies. In the future, ctDNA testing could help healthcare professionals understand whether treatment is effective far sooner than current methods allow.
While further research is needed before ctDNA testing can be used routinely, this study marks an important step towards more responsive and tailored care for people living with metastatic breast cancer.
This research was funded by Breast Cancer Now, Cancer Research UK, the NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and the ICR and published in Clinical Cancer Research.
Pioneering research into liquid biopsies
Professor Nicholas Turner and his team at the Breast Cancer Now Research Centre at the Institute of Cancer Research, London, have been pioneering research into the use of liquid biopsy blood tests to detect breast cancer relapse and guide treatment for more than a decade.