Blood-Based Biomarkers Are Reliable Predictors of Disease Recurrence in Triple Negative Breast Cancer

August 20, 2020

Circulating tumor DNA and circulating tumor cells are usual markers for minimal residual disease in patients with triple negative breast cancer, but new research shows they are also valuable indicators of disease recurrence.

The presence of circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) in the plasma of women’s blood who have previously been treated with chemotherapy prior to their surgery for either stage 1, 2 or 3 triple negative breast cancer are major indicators for disease recurrence, according to data recently published in JAMA Oncology.

Around one-third of patients with triple negative breast cancer (TNBC) will see remission of their disease after surgery and chemotherapy, while the other two-thirds will have residual disease that puts them at high risk for relapse. ctDNA, fragmented tumor derived DNA that circulates in the bloodstream, and CTCs, tumor cells that shed from the primary tumor and circulate in the bloodstream, were hypothesized to help detect minimal residual disease (MRD) which could help oncologists assess recurrence in patients. What researchers found was that detection of ctDNA and CTCs in these patients was independently associated with TNBC recurrence, making this a marker to utilize on its own.

“A diagnosis of triple negative breast cancer is very scary to the patient. The discovery and utilization of circulating tumor DNA and circulating tumor cells to better predict recurrence, by Drs. Schneider and Radovich, has provided a huge step forward toward more certainty for treatment decision making,” said Mary Lou Smith, co-founder of the Research Advocacy Network, in a press release. “This significant scientific advancement will help personalize treatments for those still battling residual disease.”

Researchers conducted a secondary analysis of a randomized clinical trial, called the PRESERVE study, of 196 female patients looking at their distant disease–free survival (DDFS), disease-free survival (DFS) and overall survival (OS). In all three of the primary outcomes, detection of ctDNA was associated with inferior outcomes. At 24 months, DDFS probability was 56% for ctDNA-positive patients compared with 81% for ctDNA-negative patients. Similar trends were also observed when combining ctDNA and CTCs.

At 24 months, DDFS, which is the length of time after primary treatment ends and the patient survives without signs or symptoms of the cancer, probability was 52% for patients who were both ctDNA positive and CTC positive. In contrast, those that were negative in both categories had a likelihood of 89% to reach DDFS.

“Since uncovering these findings in women diagnosed with triple negative breast cancer, we have learned that others are applying this stratification of patients based on ctDNA and CTCs to other cancers, including breast and colon,” said Milan Radovich, who holds a post doctorate degree and is co-director of the Indiana University Health Precision Genomics Program, in the release.

Patients’ blood samples were collected at the time of their treatment assignment. ctDNA was sequenced utilizing the Foundation-One Liquid Assay, a minimally invasive cancer DNA analysis that is becoming a bigger part of cancer care. Moreover, these tests potentially could allow for more targeted treatments as tests discover the likelihood of recurrence in individual patients.

“This is an important step forward in the treatment of women with triple negative breast cancer, who have not had much scientific evidence to point to—until now—for treatment of their disease,” said Dr. Bryan P. Schneider, the Vera Bradley Chair of Oncology at Indiana University of Health, in the release. “We are going to use these findings and continue on until we find a treatment that works for each individual woman. This effort not only involves finding the best way to kill cancer, but to minimize side effects.”


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