Breast cancer treatment: Scientists in London have developed a blood test that uses fragments of tumour DNA to predict how well some patients with breast cancer are likely to respond to treatment, potentially helping doctors adjust therapy earlier and avoid drugs that are unlikely to work.
The test is a type of liquid biopsy that measures circulating tumour DNA (ctDNA), genetic material shed into the bloodstream by cancer cells. Researchers evaluated the approach in 167 people with advanced breast cancer, taking blood samples before treatment began and again four weeks later, after one cycle of therapy.
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In the analysis, patients with lower ctDNA levels at the outset were more likely to respond to treatment. A similar pattern was seen using the four-week sample, suggesting the test could provide an early readout of whether a therapy is working.
The study divided participants into two groups based on cancer type and tumour mutations. One group included patients whose cancers carried mutations such as ESR1, HER2, AKT1, AKT or PTEN and who received targeted therapies matched to those alterations. The second group included patients with triple-negative breast cancer, a harder-to-treat subtype that accounts for roughly 10% to 15% of breast cancer cases and generally lacks established targets for precision drugs. Those patients received a combination of olaparib, a PARP inhibitor, and ceralasertib, an ATR inhibitor.
Results were strongest in the triple-negative group. Patients with low ctDNA levels before treatment had a longer period before their cancer worsened, with progression-free survival of 10.2 months compared with 4.4 months for those with higher ctDNA. Treatment responses, measured by tumours shrinking or disappearing, were also higher: 40% among patients with low ctDNA versus 9.7% among those with higher levels.
In the targeted-therapy group, ctDNA levels before treatment also tracked with outcomes, though the relationship was less pronounced. After four weeks, however, ctDNA became a clearer signal: patients whose ctDNA was undetectable at that point had better results, with their disease controlled for a median 10.6 months, compared with 3.5 months for patients whose ctDNA remained detectable.
A similar trend appeared in the triple-negative group at four weeks. Patients whose ctDNA could no longer be detected had their disease controlled for 12 months on average, compared with 4.3 months for those who still had detectable ctDNA.
Researchers said the approach could help clinicians identify early on who is benefiting from a treatment and who may need a different strategy, such as switching drugs, combining therapies, or entering a clinical trial. They added that trials are under way to determine whether changing treatment based on these early ctDNA results improves patient outcomes.
The work was carried out by a team at the Institute of Cancer Research in London and involved clinicians at the Royal Marsden. While the study focused on advanced breast cancer, the researchers said similar testing strategies could potentially be explored in earlier-stage disease as well, where faster feedback on treatment effectiveness could also influence care decisions.