Immunotherapy has become the standard of care for treating high-risk early-stage breast cancer, but its effectiveness in shrinking tumors is limited. New biomarkers that can improve patient outcomes are urgently needed.
Now, a study led by researchers at Vanderbilt Ingram Cancer Center has found that repeated blood draws (essentially liquid biopsies) can assess and predict the evolution of anti-tumor immune responses to treatment.
This minimally invasive and cost-effective alternative to tissue biopsy provides an “accessible tool for tailoring breast cancer treatment strategies,” the researchers reported in the journal Physiology. scientific translational medicine.
Researchers performed RNA sequencing on 546 peripheral blood samples taken from 160 patients with human epidermal growth factor receptor 2 (HER2)-negative high-risk stage 2 or 3 breast cancer during treatment with chemotherapy alone or in combination with immunotherapy.
Justin Barco, Ph.D., Pharm.D., professor of medicine/pathology, microbiology, and immunology at Vanderbilt Health and corresponding author of the paper, acknowledged the contributions of several co-authors, researchers on the national I-SPY2 clinical trial, who provided blood samples among other contributions to the study.
Co-author Laura Esserman, MD, MBA, director of the Breast Care Center at the University of California, San Francisco, is the principal investigator of the I-SPY2 trial, which is evaluating novel treatment strategies for subsets of breast cancer based on their molecular signatures (biomarker signatures). Vanderbilt Health is one of 42 trial sites.
Another form of liquid biopsy, cell-free DNA testing, is routinely used in the clinic for the detection, diagnosis, and treatment monitoring of various malignancies.
Balko and colleagues sampled the transcriptome, the transcription of genes involved in the clonal expansion and activation of antitumor immune cells called T cells. They found that it predicted response to the immunotherapy drug pembrolizumab.
Although validation is needed, the new liquid biopsy “has the potential to guide immunotherapy decision-making, tailor treatment plans, and advance precision oncology, not only in[breast cancer]but potentially in other solid tumors,” the researchers concluded.
The paper’s lead author, Dr. Xiaopeng Sun, currently works at Merck. Vanderbilt Health co-authors are Andres Ocampo, Jacey Marshall, and Julia Steele, graduate students in the Vanderbilt Cancer Biology Program, and Dr. Susan Opalenik, senior research supervisor in the Balko lab.
This research was supported by National Institutes of Health grants P50CA098131, PO1CA210961, R01CA255442, U54CA274502, P30CA082103, P30CA068485, and NIH/NCI Image Grant 28XS197 P-0518835, Department of Defense’s Hopeful Era Award, Breast Cancer Research Foundation, Breast Cancer Research – Atwater Trust, Fight Against Cancer, California Breast Cancer Research Program, Give Back to Breast Cancer.
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Vanderbilt University Medical Center
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DOI: 10.1126/scitranslmed.aec2358
