Breast cancer histological grade and lymph node status are important in evaluating the prognosis of patients. This study aim to predict these factors by analyzing the heterogeneity of tumor and its adjacent stroma based on dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI). A dataset of 172 patients with surgically verified lymph node status (positive lymph nodes, n=62; negative lymph nodes, n=110) who underwent preoperative DCE-MRI and DWI examination was collected. Among them, 144 cases had available histological grade information, including 56 cases of low-grade (grade 1 and 2), and 88 samples of high-grade (grade 3). To this end, we identified six tumor subregions on DCE-MRI as well as the corresponding subregions on ADC according to their distances to the tumor boundary. The statistical and Haralick texture features were extracted in each subregion, based on which predictive models were built to predict histological grade and lymph node status in breast cancer. An area under a receiver operating characteristic curve (AUC) was computed with a leave-one-out cross-validation (LOOCV) method to assess each classifier’s performance. For histological grade prediction, the classifier using DCE-MRI features in the inner tumor achieved best performance among all the subregions with AUC of 0.859. For lymph node status, classifier based on DCE-MRI features from tumor subregion of proximal peritumoral stromal shell obtained highest AUC of 0.882 among all the regions. Furthermore, the predictions from DCE-MRI and DWI were fused, and the AUC value was increased to 0.895 for discriminating histological grade. Our results demonstrate that DCE-MRI and ADC imaging features are complementary in predicting histological grade in breast cancer.
Human epidermal growth factor receptor-2 (HER2) plays an important role in treatment strategy and prognosis determination in breast cancers. However, breast cancers are characterized by considerable heterogeneity both between and within tumors, which is a key impediment to accurately determine HER2 status for radiomic analysis. To this end, tumor heterogeneity was evaluated by unsupervised decomposition method on breast magnetic resonance imaging (MRI), in which three tumor subregions were generated terms as Input, Fast and Slow. This tumor decomposition was performed by a convex analysis of mixtures (CAM) method, which was designed according to analysis of contrast-enhancement patterns. The study retrospectively investigated 181 patients who underwent dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) examination. Among them, 124 were HER2-negative and 57 were HER2-positive status. Imaging features of texture and histogram were computed in each subregion. Multivariate logistic regression classifiers were trained and validated with leave-one-out cross-validation (LOOCV) method. An area under a receiver operating characteristic curve (AUC) was calculated to assess performance of the classifier. The classifier based on features from Fast subregion obtained an AUC of 0.802 ± 0.067 and was significantly (P = 0.0113) outperformed the classifier based on features from the whole tumors. When the predicted values from the respective classifiers were fused by weighted average, the AUC significantly increased to 0.820 ± 0.063 (P = 0.0011). The results indicate that analysis of intratumor heterogeneity through decomposing method of DCE-MRI has the potential to serve as a marker for predicting HER2 status.
Breast cancer can be classified into four molecular subtypes of Luminal A, Luminal B, HER2 and Basal-like, which have significant differences in treatment and survival outcomes. We in this study aim to predict immunohistochemistry (IHC) determined molecular subtypes of breast cancer using image features derived from tumor and peritumoral stroma region based on diffusion weighted imaging (DWI). A dataset of 126 breast cancer patients were collected who underwent preoperative breast MRI with a 3T scanner. The apparent diffusion coefficients (ADCs) were recorded from DWI, and breast image was segmented into regions comprising the tumor and the surrounding stromal. Statistical characteristics in various breast tumor and peritumoral regions were computed, including mean, minimum, maximum, variance, interquartile range, range, skewness, and kurtosis of ADC values. Additionally, the difference of features between each two regions were also calculated. The univariate logistic based classifier was performed for evaluating the performance of the individual features for discriminating subtypes. For multi-class classification, multivariate logistic regression model was trained and validated. The results showed that the tumor boundary and proximal peritumoral stroma region derived features have a higher performance in classification compared to that of the other regions. Furthermore, the prediction model using statistical features, difference features and all the features combined from these regions generated AUC values of 0.774, 0.796 and 0.811, respectively. The results in this study indicate that ADC feature in tumor and peritumoral stromal region would be valuable for estimating the molecular subtype in breast cancer.
Breast cancer, with its high heterogeneity, is the most common malignancies in women. In addition to the entire tumor itself, tumor microenvironment could also play a fundamental role on the occurrence and development of tumors. The aim of this study is to investigate the role of heterogeneity within a tumor and the surrounding stromal tissue in predicting the Ki-67 proliferation status of oestrogen receptor (ER)-positive breast cancer patients. To this end, we collected 62 patients imaged with preoperative dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for analysis. The tumor and the peritumoral stromal tissue were segmented into 8 shells with 5 mm width outside of tumor. The mean enhancement rate in the stromal shells showed a decreasing order if their distances to the tumor increase. Statistical and texture features were extracted from the tumor and the surrounding stromal bands, and multivariate logistic regression classifiers were trained and tested based on these features. An area under the receiver operating characteristic curve (AUC) were calculated to evaluate performance of the classifiers. Furthermore, the statistical model using features extracted from boundary shell next to the tumor produced AUC of 0.796±0.076, which is better than that using features from the other subregions. Furthermore, the prediction model using 7 features from the entire tumor produced an AUC value of 0.855±0.065. The classifier based on 9 selected features extracted from peritumoral stromal region showed an AUC value of 0.870±0.050. Finally, after fusion of the predictive model obtained from entire tumor and the peritumoral stromal regions, the classifier performance was significantly improved with AUC of 0.920. The results indicated that heterogeneity in tumor boundary and peritumoral stromal region could be valuable in predicting the indicator associated with prognosis.
Breast cancer is a highly heterogeneous disease both biologically and clinically, and certain pathologic parameters, i.e., Ki67 expression, are useful in predicting the prognosis of patients. The aim of the study is to identify intratumor heterogeneity of breast cancer for predicting Ki-67 proliferation status in estrogen receptor (ER)-positive breast cancer patients. A dataset of 77 patients was collected who underwent dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) examination. Of these patients, 51 were high-Ki-67 expression and 26 were low-Ki-67 expression. We partitioned the breast tumor into subregions using two methods based on the values of time to peak (TTP) and peak enhancement rate (PER). Within each tumor subregion, image features were extracted including statistical and morphological features from DCE-MRI. The classification models were applied on each region separately to assess whether the classifiers based on features extracted from various subregions features could have different performance for prediction. An area under a receiver operating characteristic curve (AUC) was computed using leave-one-out cross-validation (LOOCV) method. The classifier using features related with moderate time to peak achieved best performance with AUC of 0.826 than that based on the other regions. While using multi-classifier fusion method, the AUC value was significantly (P=0.03) increased to 0.858±0.032 compare to classifier with AUC of 0.778 using features from the entire tumor. The results demonstrated that features reflect heterogeneity in intratumoral subregions can improve the classifier performance to predict the Ki-67 proliferation status than the classifier using features from entire tumor alone.
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