NEW YORK (GenomeWeb) – In a study published online today in Science Translational Medicine, researchers from the UK and the US presented evidence that circulating tumor DNA can be used to track minimal residual disease and provide relapse clues in individuals treated for breast cancer.
Using digital PCR and somatic mutation markers identified in each individual's primary tumor, the team searched for ctDNA before and after treatment in 55 women with early-stage, localized breast cancer who received neoadjuvant chemotherapy and surgery.
The presence of ctDNA in post-treatment blood samples was linked to far higher risk of relapse, the researchers reported. Women with ctDNA-positive blood samples after surgery were roughly 12 times as prone to relapse as those without. Moreover, the presence of tumor DNA in the blood preceded recurrence symptoms by almost eight months, on average.
"We have shown how a simple blood test has the potential to accurately predict which patients will relapse from breast cancer, much earlier than we can currently," senior author Nicholas Turner, leader of the molecular oncology team at the Institute of Cancer Research, London and a consultant medical oncologist at the Royal Marsden Hospital, said in a statement.
Turner noted that the same approach offered a look at cancer mutation patterns and evolution over time — insights expected to help in applying targeted treatments.
To identify tumor-specific somatic mutations in each individual's tumor, the researchers did targeted sequencing on primary tumor DNA from 55 early-stage breast cancer patients using a custom Ion AmpliSeq breast cancer panel and the Ion PGM platform.
That approach, which focused on 14 breast cancer driver genes, picked up at least one somatic mutation marker in 43 of the tumors and two or more mutations in 12 of the tumors.
The team then used digital PCR to search for the same mutations in DNA from blood samples taken at baseline, within a few weeks of surgery, and every six months after for nearly two years for 42 of the women.
While ctDNA turned up in blood samples from 69 percent of the women prior to treatment, just 19 percent had detectable ctDNA shortly after surgery.
Relapse occurred in 86 percent of individuals in the latter group within 6.5 months, on average, the researchers found. In contrast, 20 percent of women without ctDNA post-surgery experienced relapse and the average disease-free survival time for that group exceeded the study's follow-up time.
Although a significant proportion of women who developed relapsed breast cancer did not have ctDNA in their blood immediately after surgery, 80 percent of them had ctDNA in samples taken at some point after surgery.
Moreover, the team showed that it could find new mutations in individuals with minimal residual disease through targeted Illumina HiSeq 2000 sequencing on a 273-gene panel.
Turner noted that "[i]t will be some years before the test could potentially be available in hospitals, but we hope to bring this date closer by conducting much larger clinical trials starting next year."
In a Science Translational Medicine commentary accompanying the study, Massachusetts General Hospital Cancer Center researchers Tilak Sundaresan and Daniel Haber noted that the results highlight the possibility of not only detecting ctDNA in non-metastatic breast cancer, but also using this genetic material as a longitudinal marker for recurrence.
The pair noted that similar studies are needed to evaluate women with lower risk breast cancers treated with surgery alone and to explore the possibility of using ctDNA to predict cases of late relapse.