Researchers at Lund University have validated a blood-based method for measuring circulating tumor DNA in patients with early breast cancer. The method was able to identify breast cancer patients at high risk of recurrence and detect molecular signs of relapse before the disease became clinically visible using today's standard methods.
Study at a glance: prospective observational study // quantitative investigator-initiated study // biomarker study // liquid biopsy-based monitoring // statistical associations // breast cancer // 136 patients
Researchers at Lund University have developed a blood test capable of detecting signs of breast cancer recurrence long before recurrence becomes visible on imaging or cause symptoms. It has previously been shown that this method can detect extremely small amounts of tumor DNA in blood samples with very high precision and specificity. In the current much larger study, patients were followed over time to evaluate how accurate the method could predict recurrence and monitor treatment response.
"This study shows that our blood-based method, Pathlight, which reliably measures small fragments of tumor DNA, can provide early information about how breast cancer responds to chemotherapy before surgery while also indicating whether the disease has come back after surgery," says Lao Saal, researcher at Lund University and senior author of the study, which is now published in the journal EMBO Molecular Medicine.
Among patients who later developed metastatic disease, the blood test detected signs of recurrence a median of 13.8 months before the relapse became clinically visible, and in some cases nearly four years before current methods detected the disease.
Today, recurrence is most often detected only once tumors become visible using imaging or begin causing symptoms. The new analytical method instead works by tracking tiny amounts of tumor DNA in the bloodstream. It is based on comprehensive genetic profiling of the tumor, allowing researchers to identify specific DNA alterations that arise early in cancer development.
"The method is based on the idea that every tumor has a unique genetic fingerprint. By measuring these alterations in the patient's blood, we can detect extremely small amounts of residual tumor DNA with high precision, even when a recurrence is not yet visible with today's imaging methods or has begun causing symptoms," says Lao Saal.
The technology provides less detailed information than more advanced genetic analyses, but it is also faster and more cost-effective - while still being accurate enough to measure treatment response and identify patients who will go on to develop a clinical relapse.
The study included 136 participants treated with chemotherapy and surgery for different types of breast cancer. Blood samples were collected at diagnosis, during treatment, shortly after surgery, and then regularly during follow-up for up to six years.
Key results:
- Tumor DNA could be detected in the blood of nearly 90 percent of patients before treatment began.
- In approximately 21 percent of patients, tumor DNA could still be detected after the drug treatment given before surgery.
- In 13 percent of patients, tumor DNA levels did not show a clear decline during treatment, which was strongly associated with a high risk of recurrence.
- The method provided more accurate prognostic information than pathological complete response (pCR), today's established measure of treatment response before surgery in breast cancer.
- The presence of tumor DNA in blood after surgery was strongly associated with future recurrence.
"These findings could change how breast cancer patients are monitored and treated in the future. With further research, the technology may provide opportunities to improve treatment for patients at high risk of recurrence. The method may also help us optimize treatment for patients at the lowest risk of recurrence who may be able to avoid unnecessarily intensive therapy, potentially leading to fewer side effects," says Niklas Loman, senior oncologist at Skåne University Hospital and one of the researchers involved in the study.
