Identification of HER2-over-expression, HER2-low-expression, and HER2-zero-expression statuses in breast cancer based on 18F-FDG PET/CT radiomics

Abstract

Purpose: According to the updated classification system, human epidermal growth factor receptor 2 (HER2) expression statuses are divided into the following three groups: HER2-over-expression, HER2-low-expression, and HER2-zero-expression. HER2-negative expression was reclassified into HER2-low-expression and HER2-zero-expression. This study aimed to identify three different HER2 expression statuses for breast cancer (BC) patients using PET/CT radiomics and clinicopathological characteristics.

Methods and materials: A total of 315 BC patients who met the inclusion and exclusion criteria from two institutions were retrospectively included. The patients in institution 1 were divided into the training set and the independent validation set according to the ratio of 7:3, and institution 2 was used as the external validation set. According to the results of pathological examination, all BC patients were divided into HER2-over-expression, HER2-low-expression, and HER2-zero-expression. First, PET/CT radiomic features and clinicopathological features based on each patient were extracted and collected. Second, multiple methods were used to perform feature screening and feature selection. Then, four machine learning classifiers, including logistic regression (LR), k-nearest neighbor (KNN), support vector machine (SVM), and random forest (RF), were constructed to identify HER2-over-expression vs. others, HER2-low-expression vs. others, and HER2-zero-expression vs. others. The receiver operator characteristic (ROC) curve was plotted to measure the model's predictive power.

Results: According to the feature screening process, 8, 10, and 2 radiomics features and 2 clinicopathological features were finally selected to construct three prediction models (HER2-over-expression vs. others, HER2-low-expression vs. others, and HER2-zero-expression vs. others). For HER2-over-expression vs. others, the RF model outperformed other models with an AUC value of 0.843 (95%CI: 0.774-0.897), 0.785 (95%CI: 0.665-0.877), and 0.788 (95%CI: 0.708-0.868) in the training set, independent validation set, and external validation set. Concerning HER2-low-expression vs. others, the outperformance of the LR model over other models was identified with an AUC value of 0.783 (95%CI: 0.708-0.846), 0.756 (95%CI: 0.634-0.854), and 0.779 (95%CI: 0.698-0.860) in the training set, independent validation set, and external validation set. Whereas, the KNN model was confirmed as the optimal model to distinguish HER2-zero-expression from others, with an AUC value of 0.929 (95%CI: 0.890-0.958), 0.847 (95%CI: 0.764-0.910), and 0.835 (95%CI: 0.762-0.908) in the training set, independent validation set, and external validation set.

Conclusion: Combined PET/CT radiomic models integrating with clinicopathological characteristics are non-invasively predictive of different HER2 statuses of BC patients.

Keywords: Breast cancer; HER2; PET/CT; Radiomics.

Fig. 1

The flow chart of patient enrollment

Fig. 2

Process of radiomics research

Fig. 3

ROC curves of 4 constructed radiomic models for HER2-over-expression vs. others (HER2-low-expression + HER2-zero-expression) in the training (left) and independent validation set (right)

Fig. 4

ROC curves of 4 constructed radiomic models for HER2-low-expression vs. others (HER2-over-expression + HER2-zero-expression) in the training (left) and independent validation set (right)

Fig. 5

ROC curves of 4 constructed radiomic models for HER2-zero-expression vs. others (HER2-over-expression + HER2-low-expression) in the training (left) and independent validation set (right)

Fig. 6

ROC curves of the optimal radiomic models for HER2-over-expression vs. others, HER2-low-expression vs. others, and HER2-zero-expression vs. others in the external independent set