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Elevated Circulating Tumor DNA Associated With Lower Disease-Free Survival in Breast Cancer

Circulating breast tumor cells.

In a meta-analysis now published in JAMA Network Open, elevated plasma circulating tumor DNA (ctDNA) was linked to an increased risk of relapse in patients with metastatic and locally advanced breast cancer, suggesting that ctDNA detection may help determine response to treatment and increase the possibility of early detection of progression and recurrence.

"Circulating tumor DNA is a subgroup of cell-free DNA that is present in healthy individuals and is released from nonmalignant cells, and it accounts for between 0.01% and 50% of the total cell-free DNA in patients with cancer," write the investigators, led by Carolyn Cullinane, MBBS, MCh, of the Department of General and Breast Surgery at Cork University Hospital in Wilton, Cork, Ireland. "Monitoring ctDNA levels in breast cancer has the potential to gauge response to treatment and aid in early detection of disease progression or recurrence."

Dr. Cullinane and colleagues performed a systematic review of 8 studies, which included 739 patients with early, locally advanced, or metastatic breast cancer, to evaluate the association of ctDNA with disease-free survival and relapse-free survival. For a secondary end point, the authors also collected data on trends in an early breast cancer subgroup and a metastatic or locally advanced subgroup. Data collection occurred from July 30, 2019, to October 31, 2019.

The authors found that ctDNA gene variation detection both before and after treatment was associated with shorter disease-free survival, with a hazard ratio of 4.44. Detection of ctDNA was significantly associated with reduced disease-free survival in the early breast cancer subgroup, with a hazard ratio of 8.32, and in the metastatic or locally advanced subgroup, with a hazard ratio of 1.91. The pretreatment and posttreatment plasma sample collections were analyzed in both the early and the locally advanced/metastatic groups. Pretreatment plasma detection of ctDNA was significantly associated with reduced disease-free survival, with a hazard ratio of 3.30; however, the posttreatment sample collection did not reach statistical significance (hazard ratio of 8.17).

"This meta-analysis found that ctDNA detection was associated with decreased disease-free survival and progression-free survival in patients with breast cancer. The clinical utility of ctDNA ranged from early breast cancer cohorts to patients with metastatic breast cancer with multiline drug resistance," conclude the authors. "The use of ctDNA as a clinical biomarker has the potential to identify preclinical disease recurrence in patients after breast cancer treatment. In an era of personalized medicine, ctDNA shows promise as a tool for guiding future precision medicine."

For More Information

Cullinane C, Fleming C, O'Leary DP et al (2020). Association of circulating tumor DNA with disease-free survival in breast cancer: a systematic review and meta-analysis. JAMA Netw Open, 3(11):e2026921. DOI:10.1001/jamanetworkopen.2020.26921

Image credit: Min Yu. Courtesy of the National Cancer Institute/USC Norris Comprehensive Cancer Center.

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