title: Quantification of breast tumor heterogeneity for ER status, HER2 status, and TN molecular subtype evaluation on DCE-MRI.
abstract: Recognizing molecular markers is helpful for guiding treatment plans for breast cancer. This study correlated estrogen receptor (ER), human epidermal growth factor receptor 2 (HER2), and triple-negative breast cancer (TNBC) statuses to the degree of heterogeneity on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
  
  
  
  A total of 102 biopsy-proven cancers from 102 patients between October 2010 and December 2012 were used in this study, including ER (59 positive, 43 negative), HER2 (47 positive, 55 negative), and TNBC (22 TNBC, 80 non-TNBC). At first, the tumor region was segmented by using a region growing method. Then, the region-based features were extracted by the proposed regionalization method to quantify intra-tumoral heterogeneity on breast DCE-MRI. The three-dimensional morphological features (texture features and shape feature) and the pharmacokinetic model were also extracted from the segmented tumor region. After feature extraction, a logistic regression was used to classify ER, HER2, and TNBC statuses respectively. The performances were evaluated by using receiver operating characteristic (ROC) curve analysis.
  
  
  
  The proposed region-based features achieved the accuracy of 73.53%, 82.35%, and 77.45% for ER, HER2, and TNBC classifications. The corresponding area under the ROC curves (Az) achieves 0.7320, 0.8458, and 0.8328 that were better than those of texture features, shape features, and Tofts pharmacokinetic model.
  
  
  
  The intra-tumoral heterogeneity quantified by the region-based features can be used to reflect the vasculature complexity of different molecular markers and to provide prediction information of cell surface receptors on clinical examination.
authors.affiliation: Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan.
authors.forename: Ruey-Feng
authors.initials: RF
authors.lastname: Chang
authors.affiliation: Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Hong-Hao
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan. Electronic address: ycc5566@ntu.edu.tw.
authors.forename: Yeun-Chung
authors.initials: YC
authors.lastname: Chang
authors.affiliation: Department of Surgery, National Taiwan University Hospital and Nation Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chiun-Sheng
authors.initials: CS
authors.lastname: Huang
authors.affiliation: Tu and Yuen Center for Functional Onco-Imaging, Department of Radiological Sciences, University of California, Irvine, CA, United States; Department of Radiology, E-Da Hospital and I-Shou University, Kaohsiung, Taiwan.
authors.forename: Jeon-Hor
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Computer Science and Information Engineering, National Taiwan University, Taipei, Taiwan; Graduate Institute of Biomedical Informatics, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan. Electronic address: buddylo@tmu.edu.tw.
authors.forename: Chung-Ming
authors.initials: CM
authors.lastname: Lo
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001940:Breast / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D003287:Contrast Media; D005260:Female; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008875:Middle Aged; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism*; D064726:Triple Negative Breast Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: Breast Cancer; Computer-aided diagnosis; DCE-MRI; Molecular marker