Advanced breast cancer patients with high levels of methylated DNA in their blood have shorter progression-free survival and overall survival than those with low levels, according to Johns Hopkins researchers.
A key finding of the study is that a DNA detector called cMetDNA could be used to identify patients at higher risk of the cancer recurring just four weeks after they started treatment. This would allow doctors to prescribe more aggressive treatments.
DNA methylation, an important regulator of gene transcription, is common in a variety of tumors. Now it appears that high levels are associated with patient survival as well. Gene transcription is the first step in the process of creating a protein from a gene.
The study, “Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study,” was published 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,” Kala Visvanathan, MD, MHS, said in a news release. “Our study results, although preliminary, suggest that cMethDNA has the potential to be an effective way to do this for breast cancer patients.”
Visvanathan is a 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.
Researchers examined blood samples from 141 women with advanced breast cancer who were starting a new treatment at one of seven U.S. centers. Patients were also assessed four weeks after starting treatment, and when doctors restaged the cancer. Restaging, usually performed to find out if the cancer came back or got worse after treatment, was done after a median of 12 weeks.
At each time point, blood was analyzed using the cMetDNA test. This test, which looks at circulating DNA, measures levels of methylation in six breast cancer-specific genes.
Methylation is a type of chemical flag that the body often places in DNA to prevent the expression of particular genes. The researchers looked at genes that suppress tumor growth in normal circumstances but that are often found to be methylated in cancer.
To assess how hypermethylation affected patients’ progression-free survival and overall survival, researchers divided patients by high and low levels of methylated cancer DNA in their blood. In assessing progression-free survival, they found that 71 out of 128 patients had high levels of the DNA. In assessing overall survival, they found 62 out of 129 patients with high levels.
Compared with patients with low levels, those with high levels had worse progression-free survival — 2.1 months vs. 5.8 months — and worse overall survival — 12.3 months vs. 21.7 months.
Median follow-up for the patients was 19.5 months. By the end of the study, which took seven years to complete, nearly all the women had died from the disease spreading.
“What we see is an association between shorter periods of progression-free survival and overall survival in patients whose blood has higher levels of hypermethylated DNA, and we can see this very early on, after just four weeks of treatment,” said Sara Sukumar, PhD, professor of oncology at the Johns Hopkins University School of Medicine and a member of the Kimmel Cancer Center. Sukumar developed the test along with Johns Hopkins scientist Mary Jo Fackler, PhD, and others.
More tests need to be done to determine the test’s predictive ability in women with early-stage breast cancer and to assess if the test is more accurate when patients are receiving a specific therapy.
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