Blood test offers a clearer early picture for HER2-positive breast cancer, study shows

PHERGuide presented at SABCS finds a blood test can spot and follow early HER2+ breast cancer

Researchers reported at the San Antonio Breast Cancer Symposium that a new blood test reliably found and followed early-stage HER2-positive breast cancer. The PHERGuide study used circulating tumor DNA — tiny fragments of tumor genetic material that float in blood — to detect disease and to watch how tumors responded to therapy. Investigators said the test picked up ctDNA in a clear pattern: it was more common in patients with larger or more advanced tumors, and when ctDNA levels fell during treatment the scans and biopsies tended to show the cancer shrinking. When ctDNA rose again after treatment, some patients later showed visible recurrence. That combination of early detection and real-time monitoring matters because it could give doctors a faster, less invasive way to see who is responding and who needs a change in care.

How the PHERGuide trial was run and what it revealed

The PHERGuide trial enrolled several hundred patients with localized HER2-positive breast cancer who were scheduled to receive standard therapy. Researchers collected blood samples before treatment, during therapy, and after surgery or other definitive treatment. The lab looked for tumor-specific mutations and DNA fragments known to come from HER2-driven tumors. Patients were grouped by stage and tumor size so investigators could compare how often ctDNA showed up across the spectrum of early disease.

Results showed a strong link between ctDNA detection and tumor burden. Patients with larger tumors or with cancer in nearby lymph nodes were more likely to have detectable ctDNA at diagnosis. During treatment, many patients who responded saw ctDNA levels drop quickly; in some cases the blood signal disappeared before imaging clearly showed tumor shrinkage. Conversely, a return of ctDNA occurred in a subset of patients months before doctors could confirm recurrence with scans. The study reported sensitivity and specificity measures that suggested the test was not perfect but did provide meaningful lead time for some recurrences. Researchers also tested the blood assay’s ability to track known HER2 mutations and found it reliably followed the same genetic signals over time.

What this could mean for doctors and people with HER2+ disease

For patients and doctors, the idea is simple: a blood test that shows how a tumor is behaving could cut down on guesswork. If ctDNA falls early in treatment, that is a strong sign the drug is working. If ctDNA stays high or comes back, clinicians might consider changing therapies sooner or watching more closely. Because the test uses a blood draw, it is less invasive than repeated biopsies and can be done more often than scans, which are costly and expose patients to radiation.

The study suggests ctDNA could become a useful complement to imaging and pathology, not a replacement. In the near term, the most realistic use is as an extra signal that helps doctors prioritize follow-up and adjust timing of tests. For patients, earlier warning of recurrence could mean faster treatment for small relapses that are easier to control. From a safety perspective, the approach looks low risk, but its clinical benefit depends on whether earlier action based on ctDNA actually improves outcomes — a question this study did not fully answer.

Caveats and the roadmap for broader use

The PHERGuide results are encouraging but far from definitive. The trial size, while meaningful, was not large enough to prove that acting on ctDNA improves survival. Some patients never had detectable ctDNA even with confirmed tumors, so the test would miss cases. False positives — signals that do not lead to a real recurrence — also occurred and could prompt unnecessary tests or treatments.

Researchers plan larger trials that randomize patients to ctDNA-guided care or standard follow-up to test whether early action changes outcomes. Labs will also need to standardize the assay and show it performs across different machines and patient groups. Regulators will expect evidence that using ctDNA leads to better patient outcomes before recommending it as routine care.

How PHERGuide fits into the wider story of liquid biopsies

Liquid biopsies using ctDNA have been a hot area for several years. Other teams have shown similar early detection and monitoring signals in lung, colon and other cancers, but translating that signal into treatments that improve survival has been slow. The PHERGuide study adds weight to the idea that ctDNA can work in HER2-positive breast cancer as well, which matters because HER2 disease often has targeted drugs that can be switched if a tumor stops responding.

If future trials confirm benefit, payers and hospitals will face decisions about when to pay for routine ctDNA testing and how to fit it into busy clinics. That debate will shape how quickly patients actually see the test in regular care. For now, the study is a step forward — promising, not a revolution.

Sources

• prnewswire.com