Artificial intelligence-detected HER2 strong-positive tumor proportion predicts FISH positivity and treatment response in breast cancer.

Human epidermal growth factor receptor 2 (HER2)-targeted therapies have revolutionized breast cancer treatment, necessitating standardized HER2 testing. However, current immunochemistry-based HER2 assessment faces challenges due to subjectivity and variability among observers, prompting the guidance of artificial intelligence (AI). We evaluated AI's efficacy in HER2 status assessment and treatment response prediction, especially focusing on complete and intense circumferential HER2-positive (3+) tumor cells. An AI-powered HER2 analyzer (Lunit SCOPE HER2, Lunit Inc., Seoul, South Korea) and three pathologists independently assessed HER2 3 + tumor cell proportions from whole-slide images of 191 breast cancer cases from Kyung Hee University Hospital. Logistic regression and receiver operating characteristic (ROC) curves determined predictive accuracy. AI-detected 3 + tumor cell proportions strongly correlated with fluorescent in situ hybridization (FISH) positivity (area under ROC curve [AUC]: 0.783) and pathological complete response (pCR) rates (odds ratio [OR]: 1.003-1.052), outperforming pathologists' assessments. Combining AI improved prediction accuracy of pathologists, with an AUC increased from 0.712-0.813 to 0.790-0.821 for predicting FISH positivity and median OR increased from 0.996-1.061 to 1.003-1.055 for predicting pCR. Overall, this preliminary study suggests that AI could enhance HER2 status determination and treatment response prediction, complementing traditional pathological evaluation of HER2 immunohistochemistry.