Blood Test That Detects Changes in Tumor DNA Predicts Survival in Advanced Disease

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Results of a multicenter study of 129 women with advanced breast cancer show that a blood test that spots cancer-linked DNA correctly predicted that most of those patients with higher levels of the tumor markers died significantly earlier than those with lower levels.

The Johns Hopkins Kimmel Cancer Center scientists, who developed the test and led the study, say the results, if confirmed in more studies, suggest that the DNA detector, called cMethDNA, could be widely used to identify breast cancers at higher risk for recurrence and track the success or failure of treatment. Results of the study were published online Nov. 21 in the Journal of Clinical Oncology.

“There’s a great need in cancer patients to be able to quickly and easily assess if a particular treatment is working in order to switch to another if it’s not, thus avoiding wasted time, potential side effects and cost,” said Kala Visvanathan, professor of epidemiology at the Johns Hopkins Bloomberg School of Public Health, professor of oncology at the Johns Hopkins University School of Medicine and director of the Clinical Cancer Genetics Program at the Johns Hopkins Kimmel Cancer Center. “Our study results, although preliminary, suggest that cMethDNA has the potential to be an effective way to do this for breast cancer patients.”

For the biomarker study, the Johns Hopkins scientists prospectively analyzed blood samples collected from 141 women with advanced breast cancer who were beginning a new treatment at seven cancer centers in the U.S., including The Johns Hopkins Hospital.

The scientists collected the samples at the start of therapy, four weeks later and when the women’s cancers were “restaged,” usually after 12 weeks.

The cMethDNA test analyzes a filtered portion of the blood called serum, which contains proteins and genetic material, such as DNA, released by cells. The test searches for evidence of so-called hypermethylation, a type of chemical tag affixed to DNA in one or more of six breast cancer-specific genes. Biologically, hypermethylation often silences genes that keep runaway cell growth in check, and its appearance in the DNA code of breast cancer-related genes shed into the blood may indicate that a patient’s cancer growth is increasing and the disease has worsened.

To figure out how well the test reflected disease trends, results of the blood tests were analyzed to look at two measures of survival: progression-free and overall survival over the study period. The scientists then used statistical models to evaluate the distribution of cancer-linked DNA in the patients’ blood samples over the seven-year study to find the largest degree of differences between patients with low and high levels of evidence of hypermethylation in their DNA.

Because progression-free and overall survival are distinct outcomes, the cutoff value for women with high versus low levels of cancer DNA in their blood in relation with the outcome was different for progression-free and overall survival. Therefore, the absolute number of women with high and low levels of cancer DNA in their blood in the analysis of progression-free survival was different from that of the overall survival analysis.

Among 128 of the 141 patients, the scientists found that the median progression-free survival of 71 patients identified with high levels of cancer DNA in their blood was 2.1 months, compared with 5.8 months for 57 patients with low levels. In 129 patients, median overall survival for 62 patients identified with high levels of cancer DNA in their blood was 12.3 months, compared with 21.7 for 67 patients with low levels. Median follow-up of the women in the study was 19.5 months (range 0.8-86.3 months). By the end of the seven-year study period, nearly all the women enrolled in the study had died of their metastatic cancer.

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