Breast cancer is one of the most prevalent cancers in the world. The World Health Organization (WHO) says that there were an estimated 2.3 million women diagnosed with breast cancer in 2022. It also caused 6,70,000 deaths across the globe. One of the ways to improve treatment outcomes is diagnosing the disease at an early stage. With the right treatment at the appropriate time, breast cancer can be cured. While treatment options have improved, it is difficult to understand which treatment will work best for each patient.
Scientists have now developed a DNA blood test that can predict how well patients with breast cancer will respond to treatment. The new study found a blood test that can predict how well patients with advanced breast cancer will respond to targeted therapies. The study was conducted by a team of researchers from The Institute of Cancer Research, London and published in the journal Clinical Cancer Research.
The researchers used a liquid biopsy to detect the presence of tiny amounts of cancer DNA in the blood samples from 167 patients; at the start of treatment, and four weeks into the treatment. Then they compared the levels of this DNA with patients' results, which included how long it took for a cancer to grow, and how well the cancer was responding to treatment. This test can help doctors offer treatment options to patients, improving their treatment outcomes.
For the test, the researchers analysed circulating tumour DNA (ctDNA), which is released by cancer cells into the blood of patients. They found a link between low levels of ctDNA at the start of treatment, and treatment response. They also found a similar link when the results were taken at four weeks.
Dr Iseult Browne, a clinical research fellow at the ICR and first author of a study, said, "Our study shows that a simple blood test measuring circulating tumour DNA can provide an early prediction of whether a patients' breast cancer will respond to treatment. Knowing this at the earliest stage - in this case, at the start of treatment, or after just four weeks - means that we can avoid giving patients drugs that won't work and provide them with alternatives before their cancer has a chance to grow.
"For example, they could be given an alternative targeted therapy, a combination of drugs, or even enrolled into a clinical trial to test a novel drug. Trials are now under way to see if adapting a patient's treatment based on these early blood tests does indeed improve their outcome - giving them more time of living well with their cancer kept at bay."
For the study, the researchers divided the participants into two groups depending on the type of breast cancer and mutations they had. The first group had patients whose cancer had ESR1, HER2, AKT1, AKT or PTEN mutations, and who received targeted treatments matched to those mutations. The other group consisted of people with triple negative breast cancer. They received a combination of the PARP inhibitor olarparib, and the ATR inhibitor ceralasertib. For patients in the second group, low ctDNA levels before treatment began were associated with longer progression-free survival - 10.2 months, compared with 4.4 months. In this group, the percentage of patients who responded to treatment - either seeing their tumours shrink or disappear - was 40%, for those with low ctDNA levels, compared with 9.7% for those with higher levels.
A similar, but weaker, association was also observed between pre-treatment ctDNA levels and clinical outcomes in the first group.
After just four weeks of treatment, patients in the first group with undetectable ctDNA went on to have particularly good outcomes. Their cancer was kept at bay for 10.6 months, compared with 3.5 months for those whose ctDNA was still detectable. In the second group, the blood test after four weeks of treatment also showed a strong link between ctDNA levels and patient outcomes. Patients whose ctDNA was no longer detectable had their cancer kept at bay for 12 months, compared with 4.3 months in patients who still had detectable ctDNA. Treatment response was also significantly higher for those with undetectable ctDNA.
Professor Nicholas Turner, Professor of molecular oncology at ICR, and consultant medical oncologist at The Royal Marsden NHS Foundation Trust, and study lead, said, "This research looked at advanced breast cancer, but these tests could also work for early-stage breast cancers." He also added that the liquid biopsy "has the potential to make treatment decisions faster, more personalised and ultimately more effective."
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