Abstract 6468: Biopsy site-specific variation in immune signatures identified by RNA profiling in breast cancer

作者：Smruthy Sivakumar, Ericka M. Ebot, Douglas I. Lin, Meagan Montesion, Jeffrey S. Ross, Lee A. Albacker, Garrett M. Frampton, Michelle M. Williams, Ethan S. Sokol · 发表于：Cancer Research · 年份：2026 · DOI：10.1158/1538-7445.am2026-6468 · 研究领域：Cancer Immunotherapy and Biomarkers、Ferroptosis and cancer prognosis、Cancer Genomics and Diagnostics

Abstract Background: Breast cancer is generally considered to be immune cold; however, emerging data indicate heterogeneity in its immune landscape. Triple negative and HER2-positive tumors typically show higher immune cell infiltration than hormone receptor-positive (HR+) tumors. Additionally, the local microenvironment at the biopsy site may influence the immune profile of the tumor, contributing to distinct immunophenotypes. In this study, we used gene expression profiling to evaluate biopsy site-specific patterns of immune activity in breast cancer. Methods: Tumor tissue from 1,009 patients with breast cancer (all-comers) underwent targeted RNA profiling using a laboratory-developed test, FoundationOne®RNA, as part of routine clinical care. Scores for immune and stromal gene sets were generated using a single-sample gene set enrichment analysis (ssGSEA) using a research use algorithm. K-means clustering of Z-normalized scores identified two immunophenotypes: immune-high and immune-low. Samples with a negative silhouette width were classified as unknown phenotype. Results: The most common sample sites were breast (n=363), liver (n=142), lymph node (n=120), bone (n=81), and lung (n=55). Immune ssGSEA scores varied significantly by sample site. Brain biopsies (n=23) exhibited the lowest immune scores, with only 5% (1/23) classified as immune-high, whereas lymph node and lung biopsies showed higher immune scores, with 42% (51/120) and 47% (26/55) classified as immune-high, re...