By the Blouin News Science & Health staff

Tumor DNA in the blood shows cancer response to treatment

by in Fitness & Wellbeing, Medicine, Research.

Dr. Fatou Soro Ouattara of the Association of Women Researchers in the Ivory Coast (AFEMC-CI) works in her laboratory at the Institut Pasteur in Abidjan, Ivory Coast on March 5, 2013.

Dr. Fatou Soro Ouattara of the Association of Women Researchers in the Ivory Coast (REUTERS/Thierry Gouegnon)

Breast cancer is the third most common cancer in the United States, after skin and lung cancer, and kills more women than any other cancer, second only to lung cancer. The American Cancer Society estimates that more than 230,000 new cases with invasive breast cancer will be diagnosed in 2013 and that, of all women with cancer, 30% are suffering from breast cancer.

However, it is not the breast tumor itself that is lethal, but its metastasis i.e. the dissemination of the breast tumor (primary site) to other parts of the body (secondary, metastatic sites) via blood circulation. Current medical tests, such as computed tomography (CT scans) or detection of biomarkers, such as CA 15-3, are not very accurate and do not reflect patient’s condition as the total mass of tumors cannot be assessed. And biopsies, which require surgery, are impractical to be taken on a monthly basis. Over 90% of individuals with metastatic breast cancer will not survive, as there are high possibilities that a treated cancer will recur.

There is a lot of research in biomarker discovery. However, cancer is very heterogeneous and the blood consists of numerous different factors (cells, secreted proteins, etc.) Because of this, the small changes in protein levels are not easily detected by the current techniques.

Since the genetic material of the tumor is mutated, it can be easily distinguished from healthy cell DNA. Dr. Dawson and colleagues from Cancer Research UK Cambridge Institute, University of Cambridge, UK, drew blood from 30 women with metastatic breast cancer every 3 weeks over the course of 2 years. These women were all under active breast cancer treatment and had somatic genomic mutations, which are the cause for 85% of all breast cancers, in either the PIK3CA or TP53 genes. These mutations could be used to track and monitor DNA from tumor cells. The research team used two sensitive methods to isolate the circulating DNA in the blood and to sequence it. They have detected tumor DNA in 29 out of 30 women and in about 80% of all blood samples.

What was intriguing was that the levels of circulating tumor DNA were fluctuating during the course of the study, corresponding to the response to treatment. When a cancer cell is killed by a drug, its DNA is released in the blood. Thus, the more cancer cells die by a treatment, the more of the mutated DNA will be identified in the blood by these sequencing techniques. Interestingly, when the research team compared their methods with the current state of the art method to assess the response to cancer treatment, the CA 15-3 biomarker assay, detection of circulating tumor DNA provided a more reliable way for treatment assessment and disease progression. In these comparisons, circulating tumor DNA was detected in 95% of women tested with fluctuations corresponding to the treatment, while CA 15-3 assay had a less dynamic range and did not correlate well with treatment changes in about 42% of the women in the study.

However, and that is the limitation of this method, prior knowledge of which mutations each individual tumor carries is a prerequisite. This means that each patient should be screened for cancer mutations and maybe have the entire genome sequenced. Nevertheless, it is the first study that shows the potential of screening for mutated cancer DNA circulating in the blood.

The results of this study are similar to the results of de Albuquerque and colleagues from Nietzsche, Germany, who developed a method to isolate circulating tumor cells from blood of colorectal cancer patients who underwent chemotherapy. Their results correlated well with the survival of patients, but the Dawson et al. study was superior as a method of monitoring cancer treatment.  In the former study, which is using special immuno-magnets that attach to cancer cells and the PCR to detect gene markers, 65.0% of colorectal cancer patients were positive for circulating tumor cells. While in the latter study, which is using the latest advances in deep sequencing, 96% of patients were positive for circulating tumor DNA. 

Searching for circulating tumor DNA from cancer cells which have been destroyed by the therapy could become a useful strategy for the physician to assess the condition of a treated patient and decide whether the treatment is efficient, just by a blood test. As stated by medical doctors Marc Lippman and C. Kent Osborne, who did not participate in the study, such strategies could monitor the progress of additional cancer mutations that might occur during tumor progression.

Overall, these studies highlight that it is possible to complement, and maybe in the future replace entirely, the traditional tests for metastatic cancer therapy assessment and patient prognosis, with cost-effective detection of circulating tumor DNA via blood tests.