Multimodal PA/US imaging and radiomics for the prediction of HER2-zero, -low, and -positive breast cancers: A novel approach for targeted therapy selection

This study evaluates the efficacy of photoacoustic/ultrasound (PA/US) imaging-based radiomics for distinguishing HER2-zero, HER2-low, and HER2-positive breast cancer (BC), aiming to enhance targeted therapy selection. We analyzed 346 pathologically confirmed BC patients who underwent multimodal PA/US imaging at Shenzhen People’s Hospital from January 2022 to January 2025. HER2 status was determined pathologically and classified into three levels. Radiologists assessed conventional US features and manually segmented tumors on PA-images for radiomics feature extraction. Using the Least Absolute Shrinkage and Selection Operator analysis, we developed radiomics models for differentiating between HER2-zero versus HER2-low/positive cancers (Task 1), and HER2-low versus positive cancers (Task 2), and HER2-zero versus low cancers (Task 2). Patients were randomly divided into training sets and testing sets. Multivariate logistic regression was used to integrate radiomics, clinical-pathological, and US features into nomograms. In testing set, radiomics features demonstrated an AUC of 0.846 with sensitivity of 79.3% and specificity of 72.7% for Task 1, and an AUC of 0.801 with sensitivity of 64.0% and specificity of 82.8% for Task 2, and an AUC of 0.767 with sensitivity of 80.7% and specificity of 72.7% for Task 3. For Task 1, 2 and 3, nomograms including PA imaging radiomics features combined with clinical-pathological features achieved AUCs of 0.848, 0.881 and 0.780, respectively. PA radiomics features effectively differentiate between HER2-zero and HER2 low/positive, and between HER2-low and HER2-positive BC, offering potential utility in guiding targeted therapy decisions. This study demonstrates the potential of PA imaging-based radiomics for accurately classifying HER2 expression statuses in BC, enhancing the selection process for targeted therapies. By integrating multi-modal imaging and pathology data, the developed radiomics models show robust performance, promising a non-invasive diagnostic supplementary for clinical application where traditional methods are limited. • This study validates PA imaging-based radiomics as an innovative non-invasive diagnostic tool for distinguishing between different HER2 (-zero, -low, -positive) expression statuses in BC, offering a potential supplementary where traditional methods fall short. • By integrating PA radiomics with US and pathological data, the developed models enhance the accuracy of classifying HER2-zero, HER2-low and HER2-positive breast cancers, demonstrating robust performance across training and testing cohorts. • The findings support the use of PA radiomics in clinical settings to aid in the selection of appropriate HER2-targeted therapies, particularly beneficial for patients with inconclusive IHC results or when FISH is not available.