Simple DNA blood test can predict breast cancer treatment success

A simple DNA test using circulating tumour DNA could forecast how advanced breast cancer responds to treatment, enabling earlier switches to options more likely to work, researchers say.

The test analyses circulating tumour DNA (ctDNA) (tiny fragments of cancer DNA in the blood) to indicate whether a patient is likely to benefit from a specific therapy.

It could help patients avoid ineffective drugs and move sooner to alternatives, the team said.

Dr Iseult Browne, clinical research fellow at the ICR and first author, 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.”

Researchers at the Institute of Cancer Research, London (ICR) measured ctDNA in blood from 167 people with advanced breast cancer before treatment and again four weeks later, after one cycle.

There was a strong association between lower ctDNA at the start of treatment and response. A similar pattern was seen with results taken at four weeks.

The study split patients into two groups based on cancer type and mutations. One group (with ESR1, HER2, AKT1, AKT or PTEN mutations) received matched targeted therapies.

The second group, with triple negative breast cancer, received olaparib (a PARP inhibitor) plus ceralasertib (an ATR inhibitor), drugs that impair cancer cells’ DNA repair.

Among the triple negative group, low pre-treatment ctDNA was linked to longer progression-free survival: 10.2 months versus 4.4 months. Response rates were 40 per cent with low ctDNA versus 9.7 per cent with higher levels.

A weaker but similar association was seen pre-treatment in the mutation-matched group. After four weeks, those with undetectable ctDNA had better outcomes: 10.6 months without progression versus 3.5 months if ctDNA was still detectable.

In the triple negative group, undetectable ctDNA at four weeks was also associated with longer control of disease: 12 months versus 4.3 months.

Browne said: “By analysing circulating tumour DNA in blood samples from patients with advanced breast cancer, we identified a clear link between these levels, both at the start and after one cycle of treatment, and how well patients responded to therapy.

“These findings support the use of ctDNA as a non-invasive biomarker for predicting outcomes and monitoring treatment response.”

Prof Nicholas Turner, professor of molecular oncology at the ICR and consultant medical oncologist at the Royal Marsden, added “This research looked at advanced breast cancer, but these tests could also work for early-stage breast cancers.”

He added that the liquid biopsy “has the potential to make treatment decisions faster, more personalised and ultimately more effective.”