Liquid Biopsy Predicts Immunotherapy Response in Breast Cancer

Immunotherapy is now used for high-risk, early-stage breast cancer, but many tumors do not shrink and clinicians lack timely biomarkers to steer care. Serial tissue sampling is invasive, prompting interest in minimally invasive blood-based assays. Liquid biopsy strategies that capture dynamic immune activity may help identify responders earlier in treatment. A new study shows that repeated transcriptome profiling from peripheral blood can anticipate response to immunotherapy in breast cancer.

Researchers at Vanderbilt-Ingram Cancer Center (Vanderbilt University Medical Center) evaluated repeated blood sampling—essentially a liquid biopsy—as an alternative to tissue biopsy. The method applies RNA sequencing to peripheral blood to measure the transcriptome linked to clonal expansion and activation of antitumor T cells. Tracking these immune signals over time during therapy provides a readout of the evolving antitumor response.

In the study, investigators performed RNA sequencing on 546 peripheral blood samples from 160 patients with high-risk, stage 2 or 3 human epidermal growth factor receptor 2 (HER2)-negative breast cancers receiving chemotherapy alone or in combination with immunotherapy. Blood samples were contributed by investigators from the nationwide I-SPY2 clinical trial, which assesses novel treatment strategies for biomarker-defined subsets of breast cancer. Vanderbilt Health is among 42 trial locations.

The peripheral blood transcriptome predicted response to the immunotherapy drug pembrolizumab. The work also indicates that blood-based transcriptional profiling can predict tumor subtype and neoadjuvant chemoimmunotherapy outcomes. For context, cell-free DNA testing—another form of liquid biopsy—is already used clinically for detection, diagnosis, and therapeutic monitoring across malignancies.

The findings are published in Science Translational Medicine. While additional validation is needed, the authors state that this minimally invasive approach could inform immunotherapy decision-making and support treatment tailoring in breast cancer. They also note the potential relevance of this strategy to other solid tumors.

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Vanderbilt-Ingram Cancer Center