Artificial Intelligence-Powered Human Epidermal Growth Factor Receptor 2 Quantification and Clinical Outcomes in

Hongsik Kim1, Chiyoon Oum2, Soo Ick Cho2

  • 1Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, South Korea.

JCO Precision Oncology
|October 2, 2025
PubMed
Abstract

Insights

Artificial intelligence (AI) can precisely define human epidermal growth factor receptor 2 (HER2) positivity in biliary tract cancer (BTC), improving treatment outcomes. This AI approach offers a better biomarker than traditional methods for predicting response to HER2-targeted therapies.

Area of Science:

  • Oncology
  • Biomarker Discovery
  • Artificial Intelligence in Medicine

Background:

  • Current guidelines lack clear thresholds for human epidermal growth factor receptor 2 (HER2) positivity in biliary tract cancer (BTC).
  • Anti-HER2 therapies have advanced treatment for HER2-positive BTC, but precise patient selection remains a challenge.

Purpose of the Study:

  • To investigate the utility of artificial intelligence (AI) in analyzing HER2 expression and immune phenotypes (IP) for HER2-positive BTC patients receiving anti-HER2 therapy.
  • To establish AI-driven thresholds for HER2 positivity to predict treatment response.

Main Methods:

  • Post hoc analysis of a phase II trial (KCSG HB19-14) involving trastuzumab plus FOLFOX for HER2-positive BTC.
  • AI-powered quantification of HER2 expression and immune profiling on whole-slide images of pretreatment tumor samples.
  • Evaluation of clinical outcomes based on AI-defined HER2 positivity and spatial distribution of tumor-infiltrating lymphocytes.

Main Results:

  • AI-defined HER2 positivity (≥30% tumor cell proportion) significantly predicted improved progression-free survival (6.7 vs 4.9 months) and overall survival (not reached vs 8.4 months) with trastuzumab plus FOLFOX.
  • Traditional pathologist-based scoring did not stratify outcomes, unlike the AI-based continuous scoring system.
  • AI immune profiling indicated distinct immune phenotypes between HER2 3+ (immune-desert) and HER2 2+ (inflamed) tumors, suggesting implications for immunotherapy efficacy.

Conclusions:

  • AI-powered HER2 quantification offers a refined biomarker for predicting response to HER2-targeted therapies in BTC, proposing a ≥30% HER2 3+ tumor cell proportion threshold.
  • Findings suggest potential for combining anti-HER2 therapy with immune checkpoint inhibitors, guided by AI-derived immune profiling.