Liquid Biopsy Predicts Response to Breast Cancer Immunotherapy

Nashville, May 2: Researchers at the Vanderbilt-Ingram Cancer Center have identified a breakthrough approach to improving outcomes in high-risk, early-stage breast cancer, demonstrating that repeated blood sampling—known as liquid biopsy—can help assess and predict patient response to immunotherapy.

Published in Science Translational Medicine, the study highlights a minimally invasive and cost-effective alternative to traditional tissue biopsies, offering a new pathway toward personalized cancer treatment.

Led by Justin Balko, professor of Medicine and Pathology, Microbiology and Immunology at Vanderbilt Health, the research analyzed 546 blood samples from 160 patients with stage 2 and 3 breast cancers that are negative for human epidermal growth factor receptor 2 (HER2). Patients were undergoing treatment with chemotherapy alone or in combination with immunotherapy.

The team conducted RNA sequencing to study gene expression linked to the activation of T cells—key components of the body’s antitumor immune response. Findings revealed that these molecular signals in blood samples could effectively predict patient response to the immunotherapy drug Pembrolizumab.

The study was conducted in collaboration with investigators from the I-SPY2 clinical trial, a nationwide initiative exploring targeted therapies based on cancer biomarkers. Co-author Laura Esserman, director of the Breast Care Center at the University of California, San Francisco, serves as the principal investigator of the trial.

Researchers emphasized that combining molecular profiles from tissue samples with circulating tumor DNA and transcriptome data could significantly enhance treatment precision. The liquid biopsy approach allows clinicians to monitor immune response in real time and adjust therapies accordingly.

While further validation is needed, the findings suggest this approach could:

  • Guide immunotherapy decisions
  • Enable personalized treatment strategies
  • Advance precision oncology across multiple cancer types

“This method offers an accessible tool for tailoring treatment strategies in breast cancer,” the researchers noted, adding that it may also be applicable to other solid tumors.

The study underscores the growing importance of non-invasive diagnostics in oncology, paving the way for more adaptive, patient-centric cancer care.