Researchers from Lund University (Sweden) have discovered a possible new method of detecting metastases earlier than current methods allow. The novel surveillance system is based on cell-free circulating DNA (ctDNA); found in the blood circulation, ctDNA consists of small fragments of genetic material from different cells. The study, published last month in EMBO Molecular Medicine, suggests that increased ctDNA levels may predict metastasis.
Breast cancer is the current leading cause of cancer-related death in women globally; once a tumor has metastasized, the disease is frequently incurable. Metastatic breast cancer is usually only detected after becoming symptomatic, or after the tumor has grown large enough to be visible on a radiological scan. Some researchers believe that earlier detection of the disease may be clinically beneficial. However, previous attempts to test this idea have been unsuccessful, and the Lund scientists believe this may be due to use of modalities and biomarkers that lack sufficient sensitivity and/or selectivity.
For these reasons, the team, led by Lao Saal (Lund University) sought to develop an improved detection method. Using previously collected material from an ongoing breast cancer study at Lund, they analyzed the blood samples for ctDNA with the same ‘fingerprint’ as a specific tumor sample. The team believes that, although the study was small – using samples from 20 women – the findings are significant.
Saal explained that for 19 of the 20 women, the ctDNA in the blood samples provided a clear indication of the disease prognosis: “The women who never got a relapse had no detectable ctDNA, whereas all women who had tumor DNA in their blood eventually had symptomatic relapses that were diagnosed in the clinic.”
The metastases were predicted in the blood samples at an early stage, opening the possibility of detecting signs of new tumors months before hospital investigations. Saal noted: “The circulating tumour DNA values in the blood samples identified the metastases on average 11 months before they were diagnosed by standard clinical procedures. In some cases, the blood test detected the metastasis three years earlier.”
The research team have already started an expanded study with more participants, so that the existing results can be confirmed. Saal believes that if further new data do support their initial findings, the ctDNA monitoring should be performed at regular periods after breast cancer surgery.
Sources: Olsson E, Winter C, George A et al. Serial monitoring of circulating tumor DNA in patients with primary breast cancer for detection of occult metastatic disease. EMBO Mol. Med. DOI:10.15252/emmm.201404913 (2015) (Epub ahead of print); Lund University press release