Lead
On 18 January 2026, researchers at the Institute of Cancer Research in London reported a simple blood test that can predict how patients with advanced breast cancer are likely to respond to therapy. The team analysed circulating tumour DNA, or ctDNA, in blood from 167 patients before treatment and again after one cycle, about four weeks later. They found low or undetectable ctDNA at baseline and after one cycle was strongly associated with longer progression free survival and higher response rates. The result suggests clinicians could identify ineffective therapies early and offer alternatives before disease progression.
Key takeaways
- The study enrolled 167 people with advanced breast cancer and measured ctDNA before treatment and four weeks after one cycle.
- Patients with low pre-treatment ctDNA in the triple negative subgroup had a median progression free survival of 10.2 months versus 4.4 months for those with higher ctDNA.
- Response rates in the triple negative group were 40% for low pre-treatment ctDNA versus 9.7% for higher ctDNA.
- In the mutation-matched group, undetectable ctDNA at four weeks yielded a median progression free survival of 10.6 months compared with 3.5 months when ctDNA remained detectable.
- After one cycle, triple negative patients whose ctDNA became undetectable had a median progression free survival of 12 months versus 4.3 months if ctDNA persisted.
- The test uses a non-invasive liquid biopsy that assays circulating tumour DNA and may guide early treatment adaptation.
- Funders included Breast Cancer Now, Cancer Research UK, and the NIHR Biomedical Research Centre at the Royal Marsden, with the study led by ICR investigators.
Background
Breast cancer is the most common cancer worldwide, with more than 2 million new diagnoses annually. Treatment options have expanded over recent decades to include targeted agents, hormonal therapies and novel combinations, but predicting individual benefit remains challenging. Liquid biopsy techniques that detect ctDNA in plasma have matured rapidly and are under investigation as tools for monitoring response and resistance across tumour types. Clinical need is particularly acute in subgroups such as triple negative breast cancer, which accounts for about 10 to 15 percent of cases and often lacks targetable mutations.
Past studies have shown ctDNA can reflect tumour burden and emerging resistance mutations, but many efforts were limited by small cohorts or heterogeneous methods. The current study sought to test a standardized ctDNA assay across two prespecified patient groups: one receiving mutation-directed targeted therapies and a second with triple negative disease treated with a PARP inhibitor plus an ATR inhibitor. The investigators framed the assay as a predictive biomarker that could be assessed before and shortly after starting treatment to inform early decisions.
Main event
The study measured microscopic levels of ctDNA in blood samples from 167 people with advanced breast cancer. Participants were divided into two groups: a mutation-matched cohort whose tumours harboured alterations such as ESR1, HER2, AKT1 or PTEN and who received matched targeted agents, and a triple negative cohort treated with the PARP inhibitor olaparib combined with the ATR inhibitor ceralasertib. Blood draws occurred prior to therapy and again four weeks after a single treatment cycle.
Results differed by cohort but showed a consistent pattern: lower ctDNA at baseline or conversion to undetectable ctDNA after one cycle correlated with better outcomes. In the triple negative cohort, low baseline ctDNA corresponded with median progression free survival of 10.2 months versus 4.4 months for higher ctDNA, and response rates of 40 percent versus 9.7 percent. In the mutation-matched cohort the association at baseline was weaker, but undetectable ctDNA at four weeks predicted substantially longer disease control.
Investigators emphasised the assay’s potential to identify non-responders early. They suggested patients who show persistent ctDNA could be switched to alternative targeted therapies, combinations, or enrolled in clinical trials to test new agents, while those with rapid ctDNA clearance might continue the planned regimen. Trials are now underway to determine whether using ctDNA to adapt treatment actually improves survival and patient quality of life.
Analysis & implications
The study strengthens evidence that ctDNA dynamics can act as an early pharmacodynamic biomarker in advanced breast cancer, offering a window into therapeutic effect after a single cycle. If validated in randomized trials where treatment is adapted based on ctDNA results, the approach could reduce exposure to ineffective drugs, limit unnecessary toxicity, and accelerate entry into alternative strategies. Shortening the time to effective therapy may also have downstream survival and quality of life benefits, particularly for aggressive subtypes like triple negative disease.
Clinical implementation will require standardized assays, pre-specified thresholds for actionable ctDNA changes, and demonstration that actioning the test leads to better patient outcomes. There are logistical and regulatory hurdles ahead, including reimbursement, laboratory certification, and clinician training. Equity concerns must be addressed so that access to ctDNA-guided care does not widen disparities between high-resource centres and under-resourced regions.
From a scientific perspective, the study raises questions about biological heterogeneity: not all tumours shed ctDNA equally, and tumour location, size and biology influence detectability. That variability means a single ctDNA result will not perfectly classify every patient, so complementary markers and imaging will likely remain part of decision making. Finally, the strongest evidence will come from interventional trials that randomize patients to ctDNA-directed changes versus standard care.
Comparison & data
| Cohort | Pre-treatment low vs high ctDNA PFS (months) | Response rate low vs high | 4-week undetectable vs detectable PFS (months) |
|---|---|---|---|
| Mutation-matched | weaker baseline association; 4-week undetectable 10.6 vs 3.5 | not specified by baseline in detail | 10.6 vs 3.5 |
| Triple negative | 10.2 vs 4.4 | 40% vs 9.7% | 12.0 vs 4.3 |
The table condenses the principal numerical findings. In the triple negative cohort the magnitude of difference was large and consistent at baseline and at four weeks, while the mutation-matched cohort showed a clearer signal after one cycle than at baseline. These contrasts highlight that predictive performance may vary by histology and by the therapy that a patient receives.
Reactions & quotes
Lead author commentary framed the result as an early, actionable signal rather than a cure-all, and the senior investigator highlighted broader potential.
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, enabling alternatives to be offered sooner
Dr Iseult Browne, Institute of Cancer Research
Investigators noted the work focused on advanced disease but could translate to earlier stages pending further study.
The liquid biopsy has the potential to make treatment decisions faster, more personalised and ultimately more effective
Prof Nicholas Turner, Institute of Cancer Research and Royal Marsden
Unconfirmed
- Whether adapting therapy based on early ctDNA changes will definitively improve overall survival remains unproven; randomized trials are ongoing to test this strategy.
- Generalisability to early-stage breast cancer is suggested but not yet demonstrated and requires prospective validation.
- The exact ctDNA threshold values that should trigger a treatment change are not yet standardized across platforms and need consensus.
Bottom line
This study provides robust, prospective evidence that ctDNA measured before treatment and after one cycle can stratify patients with advanced breast cancer by likelihood of benefit. The clearest clinical signal was in the triple negative cohort, where baseline and early ctDNA levels correlated strongly with response and progression free survival.
Next steps must include randomized trials that test ctDNA-driven treatment changes, standardization of assays and threshold values, and planning for equitable implementation. If those steps succeed, liquid biopsy could become an early decision tool that spares patients ineffective therapy and accelerates access to better options.
Sources
- The Guardian (news article)
- Institute of Cancer Research (institutional site)
- Breast Cancer Now (charity)
- Cancer Research UK (charity and funder)
- The Royal Marsden NHS Foundation Trust (clinical partner)