ctDNA may help predict recurrence in patient with early triple-negative breast cancer

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The presence of circulating tumor DNA in early-stage triple-negative breast cancer helped predict the risk of recurrence in women who had undergone surgery after neoadjuvant chemotherapy, a study found.

The results of the study—funded by the Vera Bradley Foundation for Breast Cancer and the Indiana University Grand Challenge Precision Health Initiative—were presented at the 2019 San Antonio Breast Cancer Symposium. The trial was managed by the Hoosier Cancer Research Network and enrolled at 26 sites across the U.S.

In this study, the authors and colleagues analyzed plasma samples that had been collected from patients enrolled in the BRE12-158 clinical trial, which studied genomically directed therapy versus physician’s choice of treatment after preoperative chemotherapy in patients with triple-negative breast cancer. The trial enrolled 196 women, and ctDNA was sequenced in 142 patients using the FoundationOne Liquid Test.

Mutated ctDNA was detected in 90 of the patients, representing 63 percent. TP53 was the most commonly mutated gene, followed by others that are commonly associated with breast cancer.

At 17.2 months of follow-up, detection of ctDNA was significantly associated with inferior distant disease-free survival. Patients with ctDNA had a median DDFS of 32.5 months, while the patients without ctDNA had not reached the median.

At 24 months, the DDFS probability was 56 percent in ctDNA-positive patients, compared with 81 percent in ctDNA-negative patients. In multivariate analysis, when the researchers controlled for factors including residual cancer burden; tumor size, grade, and stage; age; and race, detection of ctDNA remained independently associated with inferior DDFS. Overall, ctDNA-positive patients were three times as likely to have distant disease recurrence than ctDNA-negative patients.

Detection of ctDNA was also associated with inferior overall survival; ctDNA-positive patients had 4.1 times increased risk of death compared with ctDNA-negative patients.

“This study establishes that triple-negative breast cancer patients who have ctDNA after neoadjuvant therapy have a higher risk of recurrence,” Schneider said. “This may set the stage for further clinical trials for these high-risk patients, evaluating novel ways to prevent recurrence.”

The authors said a clinical trial expected to begin in 2020 will further examine ctDNA’s potential in guiding therapy for those patients who are at high risk of recurrence. They also noted that sequencing technology is developing rapidly, and will likely become more sensitive and more specific over time.

“For patients who have triple-negative breast cancer with residual disease, the risk of recurrence is exceptionally high,” said the study’s senior author, Bryan P. Schneider, professor of medicine and medical and molecular genetics at Indiana University School of Medicine. “Novel therapies and technologies are critical, including those that can potentially predict the risk of relapse.”

ctDNA, or tumor DNA derived from plasma, is being explored as a way to detect cancer, guide treatment, and monitor patients during remission. The presence of ctDNA can signal the presence of cancer.

Conversely, the authors—researchers in the Indiana University Melvin and Bren Simon Cancer Center and the Vera Bradley Foundation Center for Breast Cancer Research—said that superior outcomes for those who did not have ctDNA could potentially set the stage for clinical studies evaluating the ability to reduce post-surgical treatment for these patients.

The diagnostic used in the study was Foundation Medicine’s FoundationOne Liquid Test.

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