Results from a multi-site clinical trial for patients with triple-negative breast cancer (TNBC) show that genomic testing for circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) after neoadjuvant chemotherapy can be used to detect residual disease and identify which patients could be at high risk of relapse. The results were recently published in JAMA Oncology.

The preplanned secondary analysis was conducted from March 26, 2014, to December 18, 2018, using data from 196 female patients in BRE12-158, a phase 2 multicenter randomized clinical trial that randomized patients with early-stage TNBC who had residual disease after neoadjuvant chemotherapy to receive post-neoadjuvant genomically directed therapy vs. treatment of physician choice. The study was led by the Indiana University School of Medicine and managed by Hoosier Cancer Research Network.

Genomically directed therapy looks at the tumor’s DNA to identify mutations that are targetable by FDA-approved drugs. Despite advances in breast cancer treatment and cure rates overall, TNBC remains one of the most aggressive and deadly forms of breast cancer. About 10-15% of diagnosed breast cancers are triple negative.

Researchers reported that distant disease-free survival at 2 years for ctDNA-positive patients was 56%, compared to 81% for ctDNA-negative patients. Researchers are now planning a follow-up study, called PERSEVERE.

“In this high-risk TNBC population who have residual disease after neoadjuvant chemotherapy, 63% are positive for ctDNA and 41% for CTCs. We know that patients who are positive for circulating markers have a poor prognosis,” said lead author and co-investigator Milan Radovich, PhD (pictured left), associate professor at IU School of Medicine, vice president for oncology genomics at Indiana University Health, and a researcher at the IU Simon Comprehensive Cancer Center. “What we hope to do in our upcoming PERSEVERE trial is to therapeutically intervene in these patients who are positive for ctDNA with additional genomically matched post-neoadjuvant therapy and see if we can improve outcomes.”

Both Dr. Radovich and senior author and principal investigator Bryan P. Schneider, MD (pictured right), discussed their findings in a recent JAMA Oncology podcast.

“We are very excited for the release of the correlative work from BRE12-158, which was supported by the Vera Bradley Foundation and the IU School of Medicine Precision Health Initiative,” said Dr. Schneider, Vera Bradley Professor of Oncology and a researcher at the IU Simon Comprehensive Cancer Center. “These findings are the result of collaborative work by multiple talented investigators from Indiana University and members of the Hoosier Cancer Research Network across the United States. We believe these findings have the potential to change the way all future trials in this setting should risk-stratify patients.”

See the JAMA Oncology abstract.

About Hoosier Cancer Research Network:

Hoosier Cancer Research Network (formerly known as Hoosier Oncology Group) conducts innovative cancer research in collaboration with academic and community physicians and scientists across the United States. The organization provides comprehensive clinical trial management and support, from conception through publication. Created in 1984 as a program of the Walther Cancer Institute, Hoosier Cancer Research Network became an independent nonprofit clinical research organization in 2007. Since its founding, Hoosier Cancer Research Network has conducted more than 210 trials in a variety of cancer types and supportive care, resulting in more than 350 publications. More than 8,500 subjects have participated in Hoosier Cancer Research Network clinical trials.