Blood Test Detects Breast Cancer Over a Year Before Scans

Tracking Molecular Residual Disease Through Personalized Genetic Fingerprints

Researchers tracked 1,497 blood samples collected from 136 patients across multiple treatment stages. The method, called Pathlight, searches for structural variants and large DNA rearrangements unique to each patient’s tumor. Lao Saal, senior author of the study and researcher at Lund University, explained that the test builds a unique genetic fingerprint from tumor tissue. By measuring these alterations in the blood, the system detects extremely small amounts of residual tumor DNA with high precision, even when recurrence remains invisible on standard imaging.

The study utilized digital PCR to count DNA molecules with remarkable sensitivity. The laboratory technique tracked up to 16 structural variants for each individual patient. Tumor DNA levels measured as low as 0.000136 percent, which equals roughly 1.36 parts per million. Analytical testing detected structural variants at levels as low as 0.00001 percent, while achieving 100 percent analytical specificity across thousands of control measurements to keep false positives exceptionally rare.

When Tumor DNA Refuses to Clear During Treatment

Blood samples were collected at diagnosis, during treatment, shortly after surgery, and regularly during a follow-up period lasting up to six years. The median patient age was 52, with participants ranging from 24 to 78 years old. Approximately 44.9 percent of the cohort had hormone receptor-positive and HER2-negative disease, 29.4 percent had triple-negative breast cancer, and 24.3 percent had HER2-positive disease.

While ctDNA levels dropped for most patients during chemotherapy, approximately 21 percent of patients retained detectable tumor DNA prior to surgery. Lao Saal noted that these patients faced a much higher risk of recurrence and death. Patients with persistent ctDNA showed more than triple the risk of recurrence compared to those whose ctDNA cleared entirely. Dynamic patterns proved more powerful than single measurements; patients who failed to achieve complete clearance or at least a 50 percent reduction from baseline levels experienced significantly worse outcomes, with more than half later relapsing.

Predicting Recurrence Years Before Clinical Symptoms Appear

Post-surgery monitoring revealed that rising or persistent ctDNA strongly predicted molecular relapse. Among patients who later developed distant metastatic disease, ctDNA successfully predicted recurrence in 86.7 percent of cases. When researchers examined pathologically confirmed metastases specifically, sensitivity rose to 92.9 percent.

In one case documented in the study, a 75-year-old woman with HER2-positive and hormone receptor-positive disease experienced a clearance of ctDNA during treatment and surgery. Eighteen months later, her tumor DNA signal returned while imaging scans still appeared completely normal. Clinical relapse did not manifest until nearly four years later.

Future Implications for Breast Cancer Care

Niklas Loman, senior oncologist at Skåne University Hospital and study researcher, stated that these findings could eventually alter how physicians monitor and treat breast cancer patients. With further development, the technology may optimize treatment paths—offering aggressive follow-up or additional therapies to high-risk patients while potentially sparing low-risk patients from unnecessarily intensive therapy and its associated side effects.

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