Could a Blood Test Bring Us Closer to a Cure for HER2+ Metastatic Breast Cancer?
HER2+ Research Notes | 19 October 2026
Why researchers are looking beyond scans
For people living with HER2-positive metastatic breast cancer, the hope is not simply for another reassuring result. It is for more time, more years of living well and a remission that lasts.
Some people have exceptionally long responses to HER2-directed treatment. Researchers are asking what makes those responses different … and whether looking for tiny fragments of tumour DNA in blood could help us understand them more precisely.
The important distinction is that a blood test does not treat cancer. Its potential lies in the information it may add: another way to study response, residual disease and how care might eventually become more personalised. This is promising research, not evidence that a negative test proves cure.
What is circulating tumour DNA?
Circulating tumour DNA, or ctDNA, consists of fragments of DNA released by cancer cells into the bloodstream. A blood sample can be analysed for cancer-associated genetic changes.
This is different from an ordinary blood count, liver-function test or protein tumour marker. It is also important to distinguish two uses: identifying tumour mutations that may help select a treatment, and looking for very small amounts of residual cancer after a strong response. Evidence supporting one use does not automatically validate the other.
Repeated measurements may tell researchers more than a single snapshot. However, a test can only detect DNA that reaches the sampled blood and is present above that assay’s detection threshold. No ctDNA result should be read in isolation.
Research links: ESMO ctDNA recommendations (2022)
What is Signatera?
Signatera is a personalised, tumour-informed ctDNA test. Tumour tissue is analysed to identify a set of tumour-specific DNA changes, and a customised blood assay then looks for those changes over time.
Rather than asking only whether a general cancer marker is raised, it looks for a molecular fingerprint associated with that person’s tumour. It is not a treatment, and it is not the same as an inherited-cancer-risk test.
A negative result means the tracked tumour DNA was not detected in that sample … not that every cancer cell has disappeared. Tissue availability, the amount of DNA released and the assay’s sensitivity all matter. Signatera, Guardant Reveal and research assays such as MAESTRO use different approaches; their results and sensitivity are not interchangeable.
Research links: Signatera test information · Patient information and limitations
Three different views of remission
Complete metabolic response describes a PET finding: abnormal tumour-related tracer activity has resolved according to the imaging criteria used. It does not mean that PET can see every remaining cancer cell.
Radiological complete response describes the disappearance of detectable disease according to the scan-based criteria being applied. Under RECIST 1.1, complete response includes disappearance of target lesions, with previously pathological lymph nodes reduced below the specified size threshold.
Molecular remission is a term used here for no ctDNA detected by a particular assay at a particular time. It is not a universally standardised declaration of cure.
These are complementary views, not competing verdicts. A reassuring scan and a negative blood test can both be meaningful while microscopic disease remains possible. The exact scan report, assay and clinical context matter more than a label alone.
Research links: PERCIST PET criteria (2009) · RECIST 1.1 (2009)
Exceptional responders: a clue worth studying
A 2026 MAESTRO analysis explored whether extremely sensitive ctDNA testing could distinguish exceptional from shorter responses in HER2-positive metastatic disease. Assays were successfully developed for 63 participants: 40 exceptional responders and 23 conventional responders.
Among those with year-one samples, ctDNA was detected in 0 of 27 exceptional responders, compared with 9 of 12 conventional responders. This suggests an association between very low residual disease and a lasting response.
However, this was a selected retrospective study, reported in a July 2026 medRxiv preprint that had not undergone peer review. It used MAESTRO, not Signatera. Some exceptional responders later progressed; one breast-only progression occurred despite negative molecular testing.
The finding helps generate research questions. It cannot predict an individual person’s future with certainty or show that changing treatment because of a negative result improves survival.
Research links: MAESTRO preprint (July 2026)
HEROES: testing ctDNA-guided decisions
HEROES (NCT06450314) is a French Phase II study investigating a monitored, ctDNA-guided approach in selected people with metastatic HER2-positive breast cancer whose disease has been controlled after at least two years of anti-HER2 maintenance.
The protocol uses Signatera alongside imaging. Participants with negative ctDNA may enter a planned treatment interruption with close surveillance; those with detectable ctDNA continue treatment. The study includes rules for monitoring and restarting treatment.
This describes an experimental trial strategy, not a recommendation for routine care. The question is whether molecular information can help identify a group with durable disease control while preserving safety. A trial protocol is not a positive results report.
Research links: HEROES trial record · HEROES protocol (2024)
STOP-HER2: learning from long-term response
STOP-HER2 (NCT05721248) is a Phase II study of exceptional responders whose cancer has remained controlled for at least three years on first-line anti-HER2 treatment.
It includes participants who continue treatment and participants who stop within the study, with ongoing assessments and blood-based biomarker research. These are non-randomised cohorts, so differences between the groups require careful interpretation.
Both hormone-receptor-positive and hormone-receptor-negative disease are studied; participants with hormone-receptor-positive disease continue endocrine treatment as directed by the protocol. The purpose is to learn which long responses may persist and whether biomarkers can help explain them … not to establish a negative blood test as permission to stop treatment.
Research links: STOP-HER2 trial record · Dana-Farber study details
Free-HER: encouraging, preliminary human findings
Free-HER (NCT05959291) is a single-centre pilot study in highly selected long-term responders. The original SABCS 2025 update reported 14 participants who had been in complete radiographic remission for at least 36 months and had negative ctDNA at enrolment. Median prior remission was six years.
Six used Signatera and eight used Guardant Reveal. Two developed detectable ctDNA during follow-up. One restarted anti-HER2 treatment and remained in radiographic remission; the other subsequently became ctDNA-negative without restarting.
At that report, the longest follow-up was 24 months and no deaths had occurred. This is a small conference-abstract update, subsequently published in a 2026 journal supplement … not a definitive comparative trial or proof of cure. Selection, sample size and follow-up limit what it can tell us about safety for other patients.
These are previously reported preliminary findings, not a newly discovered October breakthrough.
Research links: Free-HER original abstract (SABCS 2025) · Original SABCS abstract text · Free-HER trial record
Why a negative result needs care in bone-only disease
Bone-only metastatic breast cancer deserves a nuanced discussion. It would be incorrect to say ctDNA never works in bone-only disease.
A peer-reviewed 2025 real-world study included 778 patients, 155 with bone-only disease. In the first-line pretreatment subgroup, the proportion with detectable ctDNA did not differ significantly between bone-only and other metastatic patterns. The study used plasma tumour-fraction testing, not Signatera-based monitoring of deep remission.
That finding does not establish that a negative result during treatment excludes residual cancer in bone. A very small disease burden, variable DNA release and assay detection limits can all make a negative result difficult to interpret.
Useful questions include whether ctDNA was detectable before treatment, which assay is being used and how the result fits the scans and clinical picture. The concern is false reassurance … not an assumption that bone metastases are always invisible to blood testing.
Research links: Bone-only ctDNA study (2025)
Other studies are asking how to deepen remission
HERizon-Breast (NCT07459673) is a Phase II study of a ctDNA-guided, sequential anti-HER2 approach for newly diagnosed, de novo advanced HER2-positive disease. It combines molecular monitoring and imaging to study personalised treatment adaptation and long-term remission. The strategy remains investigational; the trial’s existence is not evidence that it has achieved a cure.
SAPPHO (NCT06439693) is a separate Phase II study in selected newly diagnosed, de novo metastatic HER2-positive patients. It evaluates an intensive sequence of HER2-directed treatments with a curative-intent research question. Curative intent describes the ambition of the study, not a demonstrated outcome.
These studies address different patient groups and different strategies. They should not be treated as interchangeable with HEROES, STOP-HER2 or Free-HER … or as options that automatically apply to someone already responding to maintenance treatment.
Research links: HERizon-Breast trial record · MSK study details · SAPPHO trial record · SAPPHO study details
Could this eventually contribute to a functional cure?
The hope is that a clearer picture of residual disease will help researchers understand who achieves unusually durable control, when additional treatment might be useful and how to personalise care without compromising longevity.
“Functional cure” is an aspiration sometimes used to describe very long-lasting control without clinically active disease. It is not a diagnosis that can currently be made from a negative ctDNA result in HER2-positive metastatic breast cancer.
To move from a promising marker to better care, studies must show more than an association with good outcomes. They need to establish that acting on the result improves outcomes or safely reduces treatment burden, with sufficiently long follow-up.
The hopeful message is that long responses are real enough to study seriously. The uncertainty is whether today’s tests can reliably identify who will remain well, for how long and under which treatment strategy.
What is established … and what remains experimental?
HER2-directed treatment, appropriate imaging and clinical review remain the foundation of care. Blood-based tumour genotyping can inform certain treatment decisions in advanced cancer, but that is not equivalent to validating ctDNA-guided treatment interruption.
Using molecular remission to change or discontinue effective HER2 maintenance remains an experimental question. The research discussed here does not justify stopping treatment based on a negative blood test.
For Australians, an overseas trial or commercially available assay does not automatically make this approach local standard care or guarantee availability or funding. Ask your oncology team whether a test would answer a useful question in your situation, whether a suitable trial is available and what would actually change after a positive or negative result.
Other useful questions are: Was my ctDNA ever detectable? How might my metastatic sites affect interpretation? Would scans continue? What are the uncertainties? A test is most useful when there is a clear, evidence-based plan for interpreting it.
Keeping the hope in perspective
This research is about understanding deeper remission and working towards longer, better lives … not asking patients to take unnecessary risks.
A negative blood test can be encouraging in context. It cannot promise a cure. The most meaningful progress will be evidence that helps more people live well for longer, with treatment decisions made together with their oncology team.
Caley x
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The complete 11-slide research note is included here in order. The cover appears at the beginning of this article, followed below by slides 2–11, including the sources page.
Sources & further reading
Primary trial records, original research and guidance are linked below. Protocols describe what researchers plan to test; they should not be read as evidence that the approach works. Trial records and eligibility may change.
Sources checked 19 October 2026. This article is general educational information, not personal medical advice. Do not stop or change effective HER2-directed treatment because of this article or a negative blood test; discuss results and treatment decisions with your oncology team.
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