Liquid biopsy may predict response to breast cancer immunotherapy, suggests study

Immunotherapy has become a standard of care in treating high-risk, early-stage breast cancers, yet it has had limited success in shrinking tumors. New biomarkers that can improve outcomes for patients are urgently needed.

Now, a study led by researchers at the Vanderbilt-Ingram Cancer Center has found that repeated blood sampling-essentially, a liquid biopsy-can assess and predict the evolving antitumor immune response to therapy.

This minimally invasive and cost-effective alternative to tissue biopsy offers “an accessible tool for tailoring treatment strategies in breast cancer,” they reported in the journal Science Translational Medicine.

The researchers performed RNA sequencing on 546 peripheral blood samples from 160 patients with high-risk, stages 2 or 3 breast cancers negative for human epidermal growth factor receptor 2 (HER2) during treatment with either chemotherapy alone or in combination with immunotherapy.

Justin Balko, PhD, PharmD, professor of Medicine and Pathology, Microbiology and Immunology at Vanderbilt Health and the paper’s corresponding author, acknowledged several co-authors — investigators from the nationwide I-SPY2 clinical trial — who, among other contributions to the study, provided the blood samples.

Co-author Laura Esserman, MD, MBA, director of the Breast Care Center at the University of California, San Francisco, is principal investigator of the I-SPY2 trial, which is assessing novel treatment strategies for subsets of breast cancer based on their molecular characteristics (biomarker signatures). Vanderbilt Health is among 42 trial locations.

Cell-free DNA testing, another form of liquid biopsy, is routinely used clinically for detection, diagnosis and therapeutic monitoring of a variety of malignancies.

Balko and his colleagues sampled the transcriptome, the transcription of genes involved in the clonal expansion and activation of antitumor immune cells called T cells. They found it predicted response to the immunotherapy drug pembrolizumab.

While validation is needed, this new liquid biopsy has the potential to “guide immunotherapy decision-making, tailor treatment regimens, and advance precision oncology, not only in (breast cancer) but potentially in other solid tumors as well,” the researchers concluded.

Reference:

Xiaopeng Sun et al. ,Peripheral blood transcriptional profiling predicts tumor subtype and neoadjuvant chemoimmunotherapy outcomes in human breast cancer.Sci. Transl. Med.18,eaec2358(2026).DOI:10.1126/scitranslmed.aec2358