Abstract
Background: Breast tumor heterogeneity is related to risk factors that lead to aggressive tumor growth; however, such heterogeneity has not been thoroughly investigated.Purpose: To evaluate the performance of texture features extracted from heterogeneity subregions on subtraction MRI images for identifying human epidermal growth factor receptor 2 (HER2) 2+ status of breast cancers.Materials and Methods: Seventy-six patients with HER2 2+ breast cancer who underwent dynamic contrast-enhanced magnetic resonance imaging were enrolled, including 42 HER2 positive and 34 negative cases confirmed by fluorescence in situ hybridization. The lesion area was delineated semi-automatically on the subtraction MRI images at the second, fourth, and sixth phases (P-1, P-2, and P-3). A regionalization method was used to segment the lesion area into three subregions (rapid, medium, and slow) according to peak arrival time of the contrast agent. We extracted 488 texture features from the whole lesion area and three subregions independently. Wrapper, least absolute shrinkage and selection operator (LASSO), and stepwise methods were used to identify the optimal feature subsets. Univariate analysis was performed as well as support vector machine (SVM) with a leave-one-out-based cross-validation method. The area under the receiver operating characteristic curve (AUC) was calculated to evaluate the performance of the classifiers.Results: In univariate analysis, the variance from medium subregion at P-2 was the best-performing feature for distinguishing HER2 2+ status (AUC = 0.836); for the whole lesion region, the variance at P-2 achieved the best performance (AUC = 0.798). There was no significant difference between the two methods (P = 0.271). In the machine learning with SVM, the best performance (AUC = 0.929) was achieved with LASSO from rapid subregion at P-2; for the whole region, the highest AUC value was 0.847 obtained at P-2 with LASSO. The difference was significant between the two methods (P = 0.021).Conclusion: The texture analysis of heterogeneity subregions based on intratumoral regionalization method showed potential value for recognizing HER2 2+ status in breast cancer.
Highlights
Breast cancer is the most common malignant tumor in women worldwide
The texture analysis of heterogeneity subregions based on intratumoral regionalization method showed potential value for recognizing human epidermal growth factor receptor 2 (HER2) 2+ status in breast cancer
There was no significant association between HER2 2+ status and patient characteristics
Summary
Breast cancer is the most common malignant tumor in women worldwide. Molecular subtypes of breast cancer, which are indicators of disease-free and overall survival, can be used to guide targeted therapy [1, 2]. A classification system based on tumor genotype categorizes breast tumors into four molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (HER2)-overexpressing, and basal-like [3,4,5,6]. HER2positive breast cancers are associated with a worse survival, a poorer prognosis, and a higher risk of recurrence than HER2negative cases; they are more sensitive to neoadjuvant trastuzumab-based therapy [12,13,14]. It is critical to identify the HER2 status of breast cancer to select the appropriate treatment and evaluate the response to therapy. Purpose: To evaluate the performance of texture features extracted from heterogeneity subregions on subtraction MRI images for identifying human epidermal growth factor receptor 2 (HER2) 2+ status of breast cancers
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