DCE-MRI based analysis of intratumor heterogeneity by decomposing method for prediction of HER2 status in breast cancer

Author(s):  
Peng Zhang ◽  
Ming Fan ◽  
Yuanzhe Li ◽  
Maosheng Xu ◽  
Lihua Li
2021 ◽  
Vol 11 ◽  
Author(s):  
Lirong Song ◽  
Chunli Li ◽  
Jiandong Yin

ObjectiveTo evaluate whether texture features derived from semiquantitative kinetic parameter maps based on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can determine human epidermal growth factor receptor 2 (HER2) status of patients with breast cancer.Materials and MethodsThis study included 102 patients with histologically confirmed breast cancer, all of whom underwent preoperative breast DCE-MRI and were enrolled retrospectively. This cohort included 48 HER2-positive cases and 54 HER2-negative cases. Seven semiquantitative kinetic parameter maps were calculated on the lesion area. A total of 55 texture features were extracted from each kinetic parameter map. Patients were randomly divided into training (n = 72) and test (n = 30) sets. The least absolute shrinkage and selection operator (LASSO) was used to select features in the training set, and then, multivariate logistic regression analysis was conducted to establish the prediction models. The classification performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsAmong the seven prediction models, the model with features extracted from the early signal enhancement ratio (ESER) map yielded an area under the ROC curve (AUC) of 0.83 in the training set (sensitivity of 70.59%, specificity of 92.11%, and accuracy of 81.94%), and the highest AUC of 0.83 in the test set (sensitivity of 57.14%, specificity of 100.00%, and accuracy of 80.00%). The model with features extracted from the slope of signal intensity (SIslope) map yielded the highest AUC of 0.92 in the training set (sensitivity of 82.35%, specificity of 97.37%, and accuracy of 90.28%), and an AUC of 0.79 in the test set (sensitivity of 92.86%, specificity of 68.75%, and accuracy of 80.00%).ConclusionsTexture features derived from kinetic parameter maps, calculated based on breast DCE-MRI, have the potential to be used as imaging biomarkers to distinguish HER2-positive and HER2-negative breast cancer.


Author(s):  
Ming Fan ◽  
Wei Yuan ◽  
Weifen Liu ◽  
Xin Gao ◽  
Maosheng Xu ◽  
...  

Abstract Objective Breast cancer is heterogeneous in that different angiogenesis and blood flow characteristics could be present within a tumor. The pixel kinetics of DCE-MRI can assume several distinct signal patterns related to specific tissue characteristics. Identification of the latent, tissue-specific dynamic patterns of intratumor heterogeneity can shed light on the biological mechanisms underlying the heterogeneity of tumors. Approach To mine this information, we propose a deep matrix factorization-based dynamic decomposition (DMFDE) model specifically designed according to DCE-MRI characteristics. The time-series imaging data were decomposed into tissue-specific dynamic patterns and their corresponding proportion maps. The image pixel matrix and the reference matrix of population-level kinetics obtained by clustering the dynamic signals were used as the inputs. Two multilayer neural network branches were designed to collaboratively project the input matrix into a latent dynamic pattern and a dynamic proportion matrix, which was justified using simulated data. Clinical implications of DMFDE were assessed by radiomics analysis of proportion maps obtained from the tumor/parenchyma region for classifying the luminal A subtype. Main results The decomposition performance of DMFDE was evaluated by the root mean square error (RMSE) and was shown to be better than that of the conventional convex analysis of mixtures (CAM) method. The predictive model with K=3, 4, and 5 dynamic proportion maps generated AUC values of 0.780, 0.786 and 0.790, respectively, in distinguishing between luminal A and nonluminal A tumors, which are better than the CAM method (AUC=0.726). The combination of statistical features from images with different proportion maps has the highest prediction value (AUC= 0.813), which is significantly higher than that based on CAM. Conclusion This proposed method identified the latent dynamic patterns associated with different molecular subtypes, and radiomics analysis based on the pixel compositions of the uncovered dynamic patterns was able to determine molecular subtypes of breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (13) ◽  
pp. 3366
Author(s):  
Anna-Sophie Liegmann ◽  
Kerstin Heselmeyer-Haddad ◽  
Annette Lischka ◽  
Daniela Hirsch ◽  
Wei-Dong Chen ◽  
...  

Purpose: Older breast cancer patients are underrepresented in cancer research even though the majority (81.4%) of women dying of breast cancer are 55 years and older. Here we study a common phenomenon observed in breast cancer which is a large inter- and intratumor heterogeneity; this poses a tremendous clinical challenge, for example with respect to treatment stratification. To further elucidate genomic instability and tumor heterogeneity in older patients, we analyzed the genetic aberration profiles of 39 breast cancer patients aged 50 years and older (median 67 years) with either short (median 2.4 years) or long survival (median 19 years). The analysis was based on copy number enumeration of eight breast cancer-associated genes using multiplex interphase fluorescence in situ hybridization (miFISH) of single cells, and by targeted next-generation sequencing of 563 cancer-related genes. Results: We detected enormous inter- and intratumor heterogeneity, yet maintenance of common cancer gene mutations and breast cancer specific chromosomal gains and losses. The gain of COX2 was most common (72%), followed by MYC (69%); losses were most prevalent for CDH1 (74%) and TP53 (69%). The degree of intratumor heterogeneity did not correlate with disease outcome. Comparing the miFISH results of diploid with aneuploid tumor samples significant differences were found: aneuploid tumors showed significantly higher average signal numbers, copy number alterations (CNAs) and instability indices. Mutations in PIKC3A were mostly restricted to luminal A tumors. Furthermore, a significant co-occurrence of CNAs of DBC2/MYC, HER2/DBC2 and HER2/TP53 and mutual exclusivity of CNAs of HER2 and PIK3CA mutations and CNAs of CCND1 and PIK3CA mutations were revealed. Conclusion: Our results provide a comprehensive picture of genome instability profiles with a large variety of inter- and intratumor heterogeneity in breast cancer patients aged 50 years and older. In most cases, the distribution of chromosomal aneuploidies was consistent with previous results; however, striking exceptions, such as tumors driven by exclusive loss of chromosomes, were identified.


Author(s):  
Dalia Abdelhady ◽  
Amany Abdelbary ◽  
Ahmed H. Afifi ◽  
Alaa-eldin Abdelhamid ◽  
Hebatallah H. M. Hassan

Abstract Background Breast cancer is the most prevalent cancer among females. Dynamic contrast-enhanced MRI (DCE-MRI) breast is highly sensitive (90%) in the detection of breast cancer. Despite its high sensitivity in detecting breast cancer, its specificity (72%) is moderate. Owing to 3-T breast MRI which has the advantage of a higher signal to noise ratio and shorter scanning time rather than the 1.5-T MRI, the adding of new techniques as diffusion tensor imaging (DTI) to breast MRI became more feasible. Diffusion-weighted imaging (DWI) which tracks the diffusion of the tissue water molecule as well as providing data about the integrity of the cell membrane has been used as a valuable additional tool of DCE-MRI to increase its specificity. Based on DWI, more details about the microstructure could be detected using diffusion tensor imaging. The DTI applies diffusion in many directions so apparent diffusion coefficient (ADC) will vary according to the measured direction raising its sensitivity to microstructure elements and cellular density. This study aimed to investigate the diagnostic accuracy of DTI in the assessment of breast lesions in comparison to DWI. Results By analyzing the data of the 50 cases (31 malignant cases and 19 benign cases), the sensitivity and specificity of DWI in differentiation between benign and malignant lesions were about 90% and 63% respectively with PPV 90% and NPV 62%, while the DTI showed lower sensitivity and specificity about 81% and 51.7%, respectively, with PPV 78.9% and NPV 54.8% (P-value ≤ 0.05). Conclusion While the DWI is still the most established diffusion parameter, DTI may be helpful in the further characterization of tumor microstructure and differentiation between benign and malignant breast lesions.


Author(s):  
Ahmet Haşim Yurttakal ◽  
Hasan Erbay ◽  
Türkan İkizceli ◽  
Seyhan Karaçavuş ◽  
Cenker Biçer

Breast cancer is the most common cancer that progresses from cells in the breast tissue among women. Early-stage detection could reduce death rates significantly, and the detection-stage determines the treatment process. Mammography is utilized to discover breast cancer at an early stage prior to any physical sign. However, mammography might return false-negative, in which case, if it is suspected that lesions might have cancer of chance greater than two percent, a biopsy is recommended. About 30 percent of biopsies result in malignancy that means the rate of unnecessary biopsies is high. So to reduce unnecessary biopsies, recently, due to its excellent capability in soft tissue imaging, Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has been utilized to detect breast cancer. Nowadays, DCE-MRI is a highly recommended method not only to identify breast cancer but also to monitor its development, and to interpret tumorous regions. However, in addition to being a time-consuming process, the accuracy depends on radiologists’ experience. Radiomic data, on the other hand, are used in medical imaging and have the potential to extract disease characteristics that can not be seen by the naked eye. Radiomics are hard-coded features and provide crucial information about the disease where it is imaged. Conversely, deep learning methods like convolutional neural networks(CNNs) learn features automatically from the dataset. Especially in medical imaging, CNNs’ performance is better than compared to hard-coded features-based methods. However, combining the power of these two types of features increases accuracy significantly, which is especially critical in medicine. Herein, a stacked ensemble of gradient boosting and deep learning models were developed to classify breast tumors using DCE-MRI images. The model makes use of radiomics acquired from pixel information in breast DCE-MRI images. Prior to train the model, radiomics had been applied to the factor analysis to refine the feature set and eliminate unuseful features. The performance metrics, as well as the comparisons to some well-known machine learning methods, state the ensemble model outperforms its counterparts. The ensembled model’s accuracy is 94.87% and its AUC value is 0.9728. The recall and precision are 1.0 and 0.9130, respectively, whereas F1-score is 0.9545.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yang Li ◽  
Su Lu ◽  
Yuhan Zhang ◽  
Shuaibing Wang ◽  
Hong Liu

Abstract Background The number of young patients diagnosed with breast cancer is on the rise. We studied the rate trend of local recurrence (LR) and regional recurrence (RR) in young breast cancer (YBC) patients and outcomes among these patients based on molecular subtypes. Methods A retrospective cohort study was conducted based on data from Tianjin Medical University Cancer Institute and Hospital for patients ≤ 35 years of age with pathologically confirmed primary invasive breast cancer surgically treated between 2006 and 2014. Patients were categorized according to molecular subtypes on the basis of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. The 5-year rates for LR, RR, and distant metastases (DM) were estimated by Kaplan-Meir statistics. Nelson-Aalen cumulative-hazard plots were used to describe local recurrence- and distant metastasis-free intervals. Results We identified 25,284 patients with a median follow-up of 82 months, of whom 1099 (4.3%) were YBC patients ≤ 35 years of age. The overall 5-year LR, RR, and DM rates in YBC patients were 6.7%, 5.1%, and 16.6%, respectively. The LR and RR rates demonstrated a decreasing trend over time (P = 0.028 and P = 0.015, respectively). We found that early-stage breast cancer and less lymph node metastases increased over time (P = 0.004 and P = 0.007, respectively). Patients with HR−/HER2+ status had a significantly higher LR (HR 20.4; 95% CI, 11.8–35.4) and DM (HR 37.2; 95% CI, 24.6–56.3) at 10 years. Breast-conserving surgery (BCS) or mastectomy did not influence rates of LR and RR. In the overall population, the 5-year survival of YBC patients exceeded 90%. Conclusions The rates of LR and RR with YBC patients demonstrated a downward trend and the proportion of early-stage breast cancer increased between 2006 and 2014. We report the highest LR rates in this young population were associated with HR−/HER2+ tumors.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qin Huo ◽  
Zhenwei Li ◽  
Siqi Chen ◽  
Juan Wang ◽  
Jiaying Li ◽  
...  

Abstract Purpose Von Willebrand Factor C and EGF Domains (VWCE) is an important gene that regulates cell adhesion, migration, and interaction. However, the correlation between VWCE expression and immune infiltrating in breast cancer remain unclear. In this study, we investigated the correlation between VWCE expression and immune infiltration levels in breast cancer. Methods The expression of VWCE was analyzed by the tumor immune estimation resource (TIMER) and DriverDB databases. Furthermore, genes co-expressed with VWCE and gene ontology (GO) enrichment analysis were investigated by the STRING and Enrichr web servers. Also, we performed the single nucleotide variation (SNV), copy number variation (CNV), and pathway activity analysis through GSCALite. Subsequently, the relationship between VWCE expression and tumor immunity was analyzed by TIMER and TISIDB databases, and further verified the results using Quantitative Real-Time PCR (RT-PCR), Western blotting, and immunohistochemistry. Results The results showed that the expression of VWCE mRNA in breast cancer tissue was significantly lower than that in normal tissues. We found that the expression level of VWCE was associated with subtypes, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status of breast cancer patients, but there was no significant difference in the expression of VWCE was found in age and nodal status. Further analyses indicated that VWCE was correlated with the activation or inhibition of multiple oncogenic pathways. Additionally, VWCE expression was negatively correlated with the expression of STAT1 (Th1 marker, r = − 0.12, p = 6e−05), but positively correlated with the expression of MS4A4A (r = 0.28, p = 0). These results suggested that the expression of VWCE was correlated with immune infiltration levels of Th1 and M2 macrophage in breast cancer. Conclusions In our study, VWCE expression was associated with a better prognosis and was immune infiltration in breast cancer. These findings demonstrate that VWCE is a potential prognostic biomarker and correlated with tumor immune cell infiltration, and maybe a promising therapeutic target in breast cancer.


2013 ◽  
Vol 71 (4) ◽  
pp. 1592-1602 ◽  
Author(s):  
Xia Li ◽  
Lori R. Arlinghaus ◽  
Gregory D. Ayers ◽  
A. Bapsi Chakravarthy ◽  
Richard G. Abramson ◽  
...  

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