Liquid Biopsy Can Predict Outcomes in Patients With Triple-Negative Breast Cancer, Researchers Say

Liquid biopsy can be used to predict outcomes in metastatic triple-negative breast cancer (TNBC), according to new research published in Journal of Clinical Oncology.

The multi-institutional team of researchers from The Ohio State University Comprehensive Cancer Center (OSUCCC), the Dana-Farber Cancer Institute, and the Broad Institute of the Massachusetts Institute of Technology and Harvard, determined that a clinically relevant liquid biopsy test can be used to profile cancer genomes from blood and predict survival outcomes for patients with metastatic TNBC.

“Although TNBC represents just 10% to 15% of all breast cancer diagnoses, the disease is responsible for 35% of all breast cancer-related deaths,” stated a release from OSUCCC. “While significant advances in understanding the genomic drivers of primary TNBC have been made in the past decade, relatively little is known about metastatic disease because surgical tumor biopsies are rarely obtained from these patients.”

TNBC is characterized by few mutations but extensive somatic copy number alterations (SCNAs); however, little is known regarding SCNAs in metastatic TNBC. According to the release, the researchers completed what is believed to be the largest genomic characterization of metastatic TNBC derived exclusively from liquid biopsies. The team measured cell-free DNA (cfDNA) in the blood and included blood samples from 164 women with metastatic TNBC who received prior chemotherapy in the neoadjuvant or metastatic setting.

Using a customized liquid biopsy technique they developed, the team distinguished levels of DNA from cancer cells and healthy cells to assess the tumor fraction. Tumor fraction of cfDNA for 96.3% of patients and SCNAs for 63.9% of patients were determined. Whole genome sequencing was performed to identify potential mutations associated with metastatic TNBC.

“Traditionally, we would need to obtain a tissue biopsy to perform the whole genome sequencing tests that could reveal potential DNA-level mutations driving a patient’s specific cancer,” Daniel Stover, MD, breast medical oncology and researcher at OSUCCC and co-first and co-corresponding author of the study, said in a statement. “For metastatic breast cancer patients, however, tissue biopsy can be risky or painful. Being able to do this type of genomic analysis from a simple blood draw allows us to get a picture of a patient’s specific cancer genomic characteristics in a less invasive way.”

Results showed that 64% of patients had more than 10% tumor DNA, the prespecified cfDNA tumor fraction threshold, which was associated with significantly worse metastatic survival (median, 6.4 months versus 15.9 months). The team also use genome-wide data to identify specific abnormal genes more frequently altered in the metastatic TNBC compared with primary cases of the disease, including chromosomal gains in drivers NOTCH2, AKT2, and AKT3. The abnormal genes were associated with survival outcomes in the patients and could serve as targets for new therapies for at-risk populations in the future, according to the team.

The team concluded that cfDNA derived from liquid biopsy offers the potential for minimally invasive genome-wide profiling of tumor alterations without tumor biopsy and can predict patient survival outcomes.

Reference

Stover D, Parsons H, Ha B, et al. Association of cell-free DNA tumor fraction and somatic copy number alterations with survival in metastatic triple-negative breast cancer. J Clin Oncol. [published online February 20, 2018]. doi/10.1200/JCO.2017.76.0033. Accessed February 22, 2018.