Scientists have developed a simple DNA blood test that could help doctors predict how well patients with breast cancer will respond to treatment, potentially transforming how the disease is managed.
Breast cancer is the world’s most commonly diagnosed cancer, affecting more than 2 million people globally each year. While treatment options have expanded significantly in recent decades, clinicians still face challenges in determining which therapies will be most effective for individual patients.
Researchers at the Institute of Cancer Research (ICR) in London have now designed a “liquid biopsy” that can assess a patient’s likelihood of responding to specific treatments even before therapy starts. By identifying patients unlikely to benefit from certain drugs early on, the test could allow doctors to switch strategies sooner, sparing patients ineffective treatments and improving overall outcomes.
The test works by analysing circulating tumour DNA (ctDNA) — tiny fragments of genetic material shed by cancer cells into the bloodstream. Scientists measured ctDNA levels in blood samples from 167 patients with advanced breast cancer, both before treatment began and again four weeks later, after a single cycle of therapy.
The study found a strong association between low ctDNA levels at the start of treatment and a positive response to therapy. A similar relationship was observed in samples taken four weeks into treatment, suggesting ctDNA levels could provide an early indicator of how well a patient is responding.
“Our study shows that a simple blood test measuring circulating tumour DNA can provide an early prediction of whether a patient’s breast cancer will respond to treatment,” said Dr Iseult Browne, a clinical research fellow at the ICR and first author of the study. “Knowing this at the earliest stage means we can avoid giving patients drugs that won’t work and offer alternative options before the cancer has a chance to grow.”
The research, funded by Breast Cancer Now, Cancer Research UK, the NIHR Biomedical Research Centre at the Royal Marsden NHS Foundation Trust and the ICR, divided patients into two groups. One group had breast cancers with specific mutations, such as ESR1, HER2, AKT1, AKT or PTEN, and received targeted therapies matched to those mutations. The second group consisted of patients with triple negative breast cancer — an aggressive subtype accounting for 10–15% of cases globally — who were treated with a combination of the PARP inhibitor olaparib and the ATR inhibitor ceralasertib.
Among patients with triple negative breast cancer, those with low ctDNA levels before treatment experienced significantly better outcomes. Their progression-free survival averaged 10.2 months, compared with 4.4 months for patients with higher ctDNA levels. Treatment response rates were also higher, with 40% of patients with low ctDNA seeing tumours shrink or disappear, compared with just 9.7% among those with higher levels.
In patients receiving targeted therapies, the link between pre-treatment ctDNA levels and outcomes was present but less pronounced. However, after four weeks of treatment, those with undetectable ctDNA went on to have notably better results, with their cancer controlled for an average of 10.6 months, compared with 3.5 months for patients whose ctDNA remained detectable.
Similar patterns were seen in the triple negative group after four weeks of therapy. Patients whose ctDNA was no longer detectable had their disease kept at bay for around 12 months, compared with 4.3 months for those with persistent ctDNA.
“These findings support the use of ctDNA as a non-invasive biomarker for predicting outcomes and monitoring treatment response,” Browne said, adding that clinical trials are now under way to test whether adapting treatment based on early blood test results can further improve patient outcomes.
Prof Nicholas Turner, professor of molecular oncology at the ICR and consultant medical oncologist at the Royal Marsden, said the approach could eventually extend beyond advanced disease. “This research looked at advanced breast cancer, but these tests could also work for early-stage breast cancers,” he said, noting that liquid biopsies have the potential to make treatment decisions faster, more personalised and ultimately more effective.
