Non-Invasive Liquid Biopsy Breakthrough Predicts Immunotherapy Success in High-Risk Breast Cancer Patients

Vanderbilt researchers developed a liquid biopsy that predicts breast cancer response to pembrolizumab. Discover how blood RNA sequencing guides immunotherapy.

By: AXL Media

Published: May 1, 2026, 6:33 AM EDT

Source: Information for this report was sourced from Vanderbilt University Medical Center

The Emerging Role of Liquid Biopsies in Early Stage Oncology

Immunotherapy has rapidly transitioned into a standard treatment for high-risk, early-stage breast cancers, yet its effectiveness in significantly shrinking tumors remains inconsistent across patient populations. To address the urgent need for better predictive tools, researchers at the Vanderbilt-Ingram Cancer Center have demonstrated that serial blood sampling, or liquid biopsy, can monitor the evolving immune response to therapy in real time. Unlike traditional tissue biopsies, which are invasive and often difficult to repeat, this method provides a continuous window into the patient’s biological reaction to treatment. The findings, published in the journal Science Translational Medicine, suggest that blood-based transcriptomics could soon play a pivotal role in personalizing breast cancer care.

Analyzing the T Cell Transcriptome to Forecast Drug Efficacy

The study focused on RNA sequencing of 546 peripheral blood samples from 160 patients participating in the nationwide I-SPY2 clinical trial. These patients presented with high-risk, stage 2 or 3 breast cancers that were negative for the HER2 protein. By sampling the transcriptome, the researchers were able to track the clonal expansion and activation of T cells, the primary drivers of the body's anti-tumor defense. The data revealed that specific genetic signatures in the blood could accurately predict whether a patient would respond to the immunotherapy drug pembrolizumab. This molecular insight allows clinicians to distinguish between patients who are benefiting from the drug and those who may require an alternative therapeutic approach.

Collaborative Research Within the I SPY2 Clinical Trial Framework

Justin Balko, PhD, PharmD, a professor at Vanderbilt Health and the study’s corresponding author, emphasized the importance of the multi-institutional collaboration that made this research possible. The blood samples were provided by the I-SPY2 trial, a large-scale initiative designed to match novel treatment strategies with specific molecular biomarkers in breast cancer subsets. Laura Esserman, MD, MBA, of the University of California, San Francisco, leads the trial, which operates across 42 locations including Vanderbilt Health. This infrastructure allowed the researchers to validate their liquid biopsy approach across a diverse and...