# Machine learning-based fusion model for predicting HER2 expression in breast cancer by Sonazoid-enhanced ultrasound: a multicenter study

**Authors:** Huiting Zhang, Manlin Lang, Huiming Shen, Hang Li, Ning Yang, Bo Chen, Yixu Chen, Hong Ding, Weiping Yang, Xiaohui Ji, Ping Zhou, Ligang Cui, Jiandong Wang, Wentong Xu, Xiuqin Ye, Zhixing Liu, Yu Yang, Tianci Wei, Hui Wang, Yuanyuan Yan, Changjun Wu, Yiyun Wu, Jingwen Shi, Yaxi Wang, Xiuxia Fang, Ran Li, Ping Liang, Jie Yu

PMC · DOI: 10.3389/fmed.2025.1585823 · Frontiers in Medicine · 2025-05-21

## TL;DR

This study uses machine learning with Sonazoid-enhanced ultrasound to predict HER2 expression in breast cancer patients, improving targeted therapy guidance.

## Contribution

A novel fusion machine learning model is proposed to predict HER2 expression using Sonazoid-enhanced ultrasound data.

## Key findings

- The fusion model achieved an AUC of 0.869 for predicting HER2 3+ cases.
- The model correctly upgraded HER2 2+ cases to HER2 3+ consistent with FISH results.
- Seven and six key features were identified for HER2 3+ and 2+/1+ prediction, respectively.

## Abstract

To predict human epidermal growth factor receptor 2 (HER2) expression in breast cancer (BC) using Sonazoid-enhanced ultrasound in a machine learning-based model.

Between August 2020 and February 2021, patients with breast cancer who underwent surgical treatment without neoadjuvant chemotherapy were prospectively enrolled from 17 hospitals in China. HER2 expression status was assessed by immunohistochemistry or fluorescence in situ hybridization (FISH). The training set contained data from 11 hospitals and the validation set contained 6 hospitals. Clinical features, B-mode ultrasound, contrast-enhanced ultrasound (CEUS), and time-intensity curve were selected by the Least Absolute Shrinkage and Selection Operator. Based on the selected features, six prediction models were established to predict HER2 3 + and 2 +/1 + expression: logistic regression (LR), support vector machine (SVM), random forest (RF), eXtreme Gradient Boosting (XGB), XGB combined with LR, and fusion model.

A total of 140 patients with breast cancer were enrolled in this study. Seven features related to HER2 3 + and six features related to HER2 2+/1 + were selected to establish prediction models. Among the six models, LR, SVM, and XGB showed the best prediction performance for both HER2 3 + and HER2 2+/1 + cases. These three models were then combined into a fusion model. In the validation, the fusion model achieved the highest value of area under the receiver operating characteristic curve as 0.869 (95%CI: 0.715–0.958) for predicting HER2 3 + and 0.747 (95%CI: 0.548–0.891) for predicting HER2 2+/1 + cases. The model could correctly upgrade HER2 2 + cases to HER2 3 + cases, consistent with the FISH test results.

Sonazoid-enhanced ultrasound can provide effective guidance for targeted therapy of breast cancer by predicting HER2 expression using machine learning approaches.

## Linked entities

- **Genes:** ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}
- **Diseases:** BC (MESH:D001943)
- **Chemicals:** Sonazoid (MESH:C069727)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12133895/full.md

## References

51 references — full list in the complete paper: https://tomesphere.com/paper/PMC12133895/full.md

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Source: https://tomesphere.com/paper/PMC12133895