Abstract PS3-12-27: Comparative analysis of the tumor immune microenvironment (TIME) and primary and metastatic tissue in HR+/HER2- and triple-negative breast cancer (TNBC)

Abstract Background: Immune checkpoint inhibitor (ICI) based regimens are standard of care for patients with TNBC and clinical trials are investigating ICI in HR+/HER2- breast cancer, with encouraging results in a subset of patients. The tumor immune microenvironment (TIME) plays a critical role in ICI response and can differ significantly by metastatic site. Given the expanding integration of ICIs in HR+/HER2- breast cancer trials, we examined the TIME across sites of disease and subtypes to illustrate how these anatomical sites are molecularly different and may impact ICI benefit. Methods: We used Tempus Lens (Tempus AI, Inc., Chicago, IL) to retrospectively analyze de-identified next-generation sequencing data from patients with HR+/HER2- breast cancer (n=6,818) and TNBC (n=2,715) in the Tempus Database. Metaplastic histology was excluded. Among HR+/HER2- breast cancer and TNBC, tumors from primary breast (PB, n=4451), liver (n=1117), bone (n=845), lymph node (LN, n=425), lung (n=388), and brain/CNS (n=234) metastatic sites were sequenced with Tempus xT DNA (648-gene panel) and xR RNA assays. TMB, MSI, PD-L1 (CPS, clone 22c3), and proportions of B, T (CD4+, CD8+), NK cells, and macrophages of immune cells via quanTIseq deconvolution were compared across metastatic sites in HR+/HER2- breast cancer and compared to TNBC. Chi-squared/Fisher’s exact or Kruskal-Wallis tests were used to assess statistical significance. Results: In this study, the median age at diagnosis in the HR+/HER2- and TNBC cohort was 58 and 57, respectively and both cohorts were diverse: White (50%/44%), African American (8%/14%), Hispanic (6.7%/7%), Asian (3.1%/2.3%), other race (5.5%/5.5%) and unknown (33%/34%). Overall, 67% of patients were stage IV. Among patients with HR+/HER2- breast cancer, brain/CNS (14%) was most commonly TMB high (≥10 mut/mB) followed by bone (9.4%) and liver (8.9%) (p=10% (positive) proportions were highest in PB (4.1%), lung (3.6%) and LN (4.9%) (p