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1. Circulating tumor DNA was found to show significantly greater sensitivity in identifying metastatic breast cancer than other circulating biomarkers.
2. Using circulating tumor DNA to monitor metastatic breast cancer allows for more specific prognosis and evaluation during treatment.
There are various treatments available for patients with breast cancer, however monitoring a patient’s response to treatment is critical to understanding the efficacy of the therapy. Current monitoring of breast cancer metastasis analyzes levels of cancer antigen 15-3 (CA 15-3) or circulating tumor cells (CTC), however these measures lack accuracy and sensitivity. This study identified circulating tumor DNA (ctDNA) in the patient’s plasma as a more specific and sensitive biomarker to analyze breast cancer metastasis. Researchers compared ctDNA analysis with both CA 15-3 and CTC to determine if there is a significant difference in sensitivity and specificity of the different biomarkers.
Of the 114 samples used to compare circulating tumor DNA with CA-15, ctDNA was identified in 82% of samples, while CA 15-3 was identified in only 62%. Similarly, out of 126 samples comparing ctDNA to CTC, ctDNA was identified in 84% compared to 60% with CTC. These findings suggest a significantly more accurate method of evaluating treatment progress for clinicians.
Click to read the study in the New England Journal of Medicine
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1. Circulating tumor DNA was found to show significantly greater sensitivity in identifying metastatic breast cancer than other circulating biomarkers.
2. Using circulating tumor DNA to monitor metastatic breast cancer allows for more specific prognosis and evaluation during treatment.
This [prospective, single-center] study looked at circulating tumor DNA fragments carrying somatic genomic alterations that are associated with tumors. Researchers identified the PIK3CA and TP53 gene sequences as two somatic genomic alteration sequences in tumor-tissue samples collected from 30 female patients. Personalized assays were developed to detect levels of circulating tumor DNA in the plasma correlating to these gene sequences. This study compares the sensitivity and specificity of circulating tumor DNA (ctDNA) to two standard biomarkers used to monitor breast cancer metastasis: cancer antigen 15-3 (CA 15-3) and circulating tumor cells (CTC).
Using a modified bootstrapping statistical method, researchers compared ctDNA to both biomarkers to identify an overall sensitivity comparison. Based on these results, ctDNA was found significantly more sensitive than CTC (90% compared to 67%). Similarly, compared to CA 15-3, ctDNA was found significantly more sensitive (85% compared to 59%). The study also reported that in greater than 60% of the samples where neither CTC nor CA 15-3 were identified, ctDNA was found present.
In sum: The findings from this study provide support for a more accurate method of monitoring breast cancer metastasis during treatment. Aside from the inherent value of a more accurate measure to evaluate treatment progress, this work also continues to support the genomic framework for segmenting patient populations and integrating genomic knowledge with clinical practice. One drawback of this study is the size of the population. Researchers were only able to identify 30 patients with matching somatic genomic alterations in their tumor-tissue samples. Further analysis investigating the use of circulating tumor DNA should consider the heterogeneity in tumor-tissue genomic alterations to achieve a more diverse sampling of circulating tumor DNA sequences.
Click to read the study in the New England Journal of Medicine
By Jordan Anderson and Andrew Bishara
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