PS4-05-21: The Molecular and Immune Landscape of HER2 Positive Breast Cancer

Abstract Background Recent molecular profiling advances have transformed breast cancer treatment. These breakthroughs have largely benefited patients with hormone receptor-positive and triple-negative breast cancers, while HER2-positive (HER2+) breast cancer remains less understood molecularly. We evaluated the tumor immune microenvironment of HER2+ breast cancer, assessing immune cell infiltration, TMB, PD-L1 status, and HLA allele prevalence, to uncover biomarkers for treatment guidance. Methods We used Tempus Lens (Tempus AI, Inc., Chicago, IL) to identify 455 female patients with HER2+ breast cancer and xT and xR testing. Patients were classified as having localized (stage 1-3, N = 124) or de novo metastatic disease (stage 4, N = 331). Wilcoxon rank sum, Fisher’s exact, and Pearson’s Chi-squared tests were used to compare groups. Immune cell proportions were estimated using quanTIseq. TMB, PD-L1, HLA, MSI, and MMR were also analyzed. Real-world progression-free survival (rwPFS) was time from therapy (neoadjuvant or first-line) start to progression. Real-world overall survival (rwOS) was time from first-line therapy start to death or loss to follow up. Median rwOS and rwPFS were estimated with Kaplan-Meier (KM) and hazard ratios (HR) using Cox proportional hazard models (CoxPh). Results In patients with localized disease, the median proportion of tumor-infiltrating B cells was significantly higher than in those with metastatic disease (p < 0.001). A similar pattern was observed for natural killer (NK) cells, CD8+ T cells, and regulatory T cells (Tregs), with enrichment in localized stage patients (p