Physicians may be able to identify several new biomarkers related to immune activation to aid in patient selection for radioembolization of breast cancer liver metastasis, according to data in “Immune activation markers and response to radioembolization of breast cancer liver metastasis: Pilot study.”
Breast cancer is the most common female cancer worldwide, and nearly 30% of women diagnosed with early-stage breast cancer develop metastatic disease, according to breastcancer.org. “My eventual goal is to find better ways to treat metastatic breast cancer,” said Amy Deipolyi, MD, PhD, FSIR, lead author on the abstract. “Radioembolization is a locoregional therapy for breast cancer liver metastasis. Most breast cancer patients achieve response to treatment, and patients who respond live longer than ones that do not.”
According to Dr. Deipolyi, the goal of the study was to define predictors of response to guide patient selection and identify targets for combination with immunotherapy. “I wanted to discover how radioembolization impacts the immune system. I surmised that radioembolization is one way to generate tumor antigens, which could drive innate antitumor immunity. Determining how radioembolization impacts immune response may reveal which types of immunotherapy would best be given concurrently as a combination strategy.”
The abstract, which was named one of the SIR 2022 Abstracts of the Year, details the data collected from a prospective single-center study, which enrolled 23 women with liver-dominant breast cancer liver metastasis who planned to undergo radioembolization with two lobar infusions.
“Though most patients achieve response to radioembolization, most will eventually progress,” said Dr. Deipolyi. “Radioembolization also has no impact on extrahepatic metastases. I was inspired by reports that radioembolization could induce abscopal effects. Specifically, there were case reports that treating liver metastases with radioembolization led to response in extrahepatic sites, by triggering systemic anti-tumor immunity. I wanted to figure out why all patients did not have abscopal effects and generate ideas about how I might induce them. Also, I wanted to determine whether there were strategies to prolong the response achieved with radioembolization.”
Researchers collected peripheral blood and liver tumor biopsy tissue prior to the first and second lobar infusions, and flow cytometry and gene expression studies were performed to assess interleukin (IL), monocyte, myeloid derived suppressor cell (MDSC) and tumor-infiltrating lymphocyte (TIL) levels. The data collected indicated that radioembolization is associated with immune activation, both within the tumor and peripherally. Among patients who achieved a complete response, higher baseline PD1+ CD4+ TILs were identified.
“Despite the small sample size, this prospective pilot study identified robust immunologic biomarkers that predicted eventual response. These biomarkers can assist in patient selection,” said Dr. Deipolyi. “We also found that PD1 activity predicted response, suggesting PD1 immunotherapy agents may be optimal in combination strategies.”
According to Dr. Deipolyi, the next step for research will be a prospective phase I/II study combining radioembolization with a PD1 checkpoint inhibitor.
