Identifying Triple-Negative Breast Cancer Using Background Parenchymal Enhancement Heterogeneity on Dynamic Contrast-Enhanced MRI: A Pilot Radiomics Study

Objectives To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE) MRI at 3.0 Tesla in identifying “triple-negative" breast cancers. Materials and Methods In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC) using cross-validation. Results Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (p<0.01). Similar improvements were seen in nearly all subtype classification tasks undertaken. Notably, amongst the most discriminating features for predicting triple-negative cancers were textures of background parenchymal enhancement. Conclusions Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype. Prospective validation studies are warranted to confirm these findings and determine potential implications.

[1]  Wilhelm Burger,et al.  Digital Image Processing - An Algorithmic Introduction using Java , 2008, Texts in Computer Science.

[2]  Savannah C Partridge,et al.  Are Qualitative Assessments of Background Parenchymal Enhancement, Amount of Fibroglandular Tissue on MR Images, and Mammographic Density Associated with Breast Cancer Risk? , 2015, Radiology.

[3]  R. Gelber,et al.  Tailoring therapies—improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015 , 2015, Annals of oncology : official journal of the European Society for Medical Oncology.

[4]  Kenneth G. A. Gilhuijs,et al.  Association between rim enhancement of breast cancer on dynamic contrast-enhanced MRI and patient outcome: impact of subtype , 2014, Breast Cancer Research and Treatment.

[5]  Rajesh Singh,et al.  TLRs: linking inflammation and breast cancer. , 2014, Cellular signalling.

[6]  W. Niessen,et al.  Quantification of Heterogeneity as a Biomarker in Tumor Imaging: A Systematic Review , 2014, PloS one.

[7]  David J Mooney,et al.  Extracellular matrix stiffness and composition jointly regulate the induction of malignant phenotypes in mammary epithelium. , 2014, Nature materials.

[8]  Jingmei Li,et al.  Digital mammographic density and breast cancer risk: a case–control study of six alternative density assessment methods , 2014, Breast Cancer Research.

[9]  Maciej A Mazurowski,et al.  Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging. , 2014, Radiology.

[10]  P. Lambin,et al.  Robust Radiomics Feature Quantification Using Semiautomatic Volumetric Segmentation , 2014, PloS one.

[11]  Maryellen L. Giger,et al.  Quantitative MRI Phenotyping of Breast Cancer across Molecular Classification Subtypes , 2014, Digital Mammography / IWDM.

[12]  P. Lambin,et al.  Decoding tumour phenotype by noninvasive imaging using a quantitative radiomics approach , 2014, Nature Communications.

[13]  A. Madabhushi,et al.  Computerized image analysis for identifying triple-negative breast cancers and differentiating them from other molecular subtypes of breast cancer on dynamic contrast-enhanced MR images: a feasibility study. , 2014, Radiology.

[14]  Y. Matsuno,et al.  Prognostic significance of pathologic complete response and Ki67 expression after neoadjuvant chemotherapy in breast cancer , 2015, Breast Cancer.

[15]  Arabinda Ghosh,et al.  Deciphering Ligand Specificity of a Clostridium thermocellum Family 35 Carbohydrate Binding Module (CtCBM35) for Gluco- and Galacto- Substituted Mannans and Its Calcium Induced Stability , 2013, PloS one.

[16]  Karla Kerlikowske,et al.  Agreement of Mammographic Measures of Volumetric Breast Density to MRI , 2013, PloS one.

[17]  Andrew H. Beck,et al.  Mammographic density and risk of breast cancer by age and tumor characteristics , 2013, Breast Cancer Research.

[18]  D. Quail,et al.  Microenvironmental regulation of tumor progression and metastasis , 2014 .

[19]  B. Yun,et al.  Quantitative analysis of breast parenchymal background enhancement (BPE) on magnetic resonance (MR) imaging: Association with mammographic breast density and aggressiveness of the primary cancer in postmenopausal women. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[20]  C. Perou,et al.  Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013 , 2013, Annals of oncology : official journal of the European Society for Medical Oncology.

[21]  M. Giger,et al.  Breast image analysis for risk assessment, detection, diagnosis, and treatment of cancer. , 2013, Annual review of biomedical engineering.

[22]  John Kornak,et al.  MRI Enhancement in Stromal Tissue Surrounding Breast Tumors: Association with Recurrence Free Survival following Neoadjuvant Chemotherapy , 2013, PloS one.

[23]  Zaver M. Bhujwalla,et al.  In Vivo “MRI Phenotyping” Reveals Changes in Extracellular Matrix Transport and Vascularization That Mediate VEGF-Driven Increase in Breast Cancer Metastasis , 2013, PloS one.

[24]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumours , 2013 .

[25]  Wendy B DeMartini,et al.  Background parenchymal enhancement on breast MRI: impact on diagnostic performance. , 2012, AJR. American journal of roentgenology.

[26]  Steven J. M. Jones,et al.  Comprehensive molecular portraits of human breast tumors , 2012, Nature.

[27]  L. Esserman,et al.  Locally advanced breast cancer: MR imaging for prediction of response to neoadjuvant chemotherapy--results from ACRIN 6657/I-SPY TRIAL. , 2012, Radiology.

[28]  F. Markowetz,et al.  The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups , 2012, Nature.

[29]  Eun-Kyung Kim,et al.  Triple-negative invasive breast cancer on dynamic contrast-enhanced and diffusion-weighted MR imaging: comparison with other breast cancer subtypes , 2012, European Radiology.

[30]  A Vignati,et al.  Computer-aided diagnosis for dynamic contrast-enhanced breast MRI of mass-like lesions using a multiparametric model combining a selection of morphological, kinetic, and spatiotemporal features. , 2012, Medical physics.

[31]  Patrick Granton,et al.  Radiomics: extracting more information from medical images using advanced feature analysis. , 2012, European journal of cancer.

[32]  Jennifer D. Brooks,et al.  Background parenchymal enhancement at breast MR imaging and breast cancer risk. , 2011, Radiology.

[33]  Bonnie N. Joe,et al.  Can signal enhancement ratio (SER) reduce the number of recommended biopsies without affecting cancer yield in occult MRI-detected lesions? , 2011, Academic radiology.

[34]  Karla Kerlikowske,et al.  Volume of Mammographic Density and Risk of Breast Cancer , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[35]  Nuria Lopez-Bigas,et al.  Gitools: Analysis and Visualisation of Genomic Data Using Interactive Heat-Maps , 2011, PloS one.

[36]  Elizabeth A Morris,et al.  Background parenchymal enhancement on baseline screening breast MRI: impact on biopsy rate and short-interval follow-up. , 2011, AJR. American journal of roentgenology.

[37]  Guilherme J. M. Rosa The Elements of Statistical Learning: Data Mining, Inference, and Prediction by HASTIE, T., TIBSHIRANI, R., and FRIEDMAN, J , 2010 .

[38]  Jorge S Reis-Filho,et al.  Triple-negative breast cancer. , 2010, The New England journal of medicine.

[39]  Jong Hyo Kim,et al.  Multilevel analysis of spatiotemporal association features for differentiation of tumor enhancement patterns in breast DCE-MRI. , 2010, Medical physics.

[40]  Ashutosh Kumar Singh,et al.  The Elements of Statistical Learning: Data Mining, Inference, and Prediction , 2010 .

[41]  R. Gillies,et al.  The biology underlying molecular imaging in oncology: from genome to anatome and back again. , 2010, Clinical radiology.

[42]  T. Nielsen,et al.  Breast cancer subtypes and the risk of local and regional relapse. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[43]  M. Giger,et al.  Cancerous breast lesions on dynamic contrast-enhanced MR images: computerized characterization for image-based prognostic markers. , 2010, Radiology.

[44]  K. Gelmon,et al.  Ki67 in breast cancer: prognostic and predictive potential. , 2010, The Lancet. Oncology.

[45]  Dmitrij Frishman,et al.  Pitfalls of supervised feature selection , 2009, Bioinform..

[46]  Anil K. Jain Data clustering: 50 years beyond K-means , 2008, Pattern Recognit. Lett..

[47]  Ian H. Witten,et al.  The WEKA data mining software: an update , 2009, SKDD.

[48]  Willem P. Th. M. Mali,et al.  Computer-aided detection (CAD) for breast MRI: evaluation of efficacy at 3.0 T , 2009, European Radiology.

[49]  Carlo Catalano,et al.  The Challenge of Imaging Dense Breast Parenchyma: Is Magnetic Resonance Mammography the Technique of Choice? A Comparative Study With X-Ray Mammography and Whole-Breast Ultrasound , 2009, Investigative radiology.

[50]  T. Uematsu,et al.  Triple-negative breast cancer: correlation between MR imaging and pathologic findings. , 2009, Radiology.

[51]  Debra L Winkeljohn Triple-negative breast cancer. , 2008, Clinical journal of oncology nursing.

[52]  C. Boetes,et al.  Breast MRI: guidelines from the European Society of Breast Imaging , 2008, European Radiology.

[53]  R. G. Stough Breast MR Imaging: Computer-aided Evaluation Program for Discriminating Benign from Malignant Lesions , 2008 .

[54]  Woo Kyung Moon,et al.  Index terms: Breast neoplasms Breast, MR , 2006 .

[55]  A. Tutt,et al.  Triple negative tumours: a critical review , 2007, Histopathology.

[56]  Kornelia Polyak,et al.  Breast cancer: origins and evolution. , 2007, The Journal of clinical investigation.

[57]  Ercan E. Kuruoglu,et al.  Image separation using particle filters , 2007, Digit. Signal Process..

[58]  M. Yaffe,et al.  American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography , 2007, CA: a cancer journal for clinicians.

[59]  Lester L. Peters,et al.  Genome-wide association study identifies novel breast cancer susceptibility loci , 2007, Nature.

[60]  N. Boyd,et al.  Mammographic density and the risk and detection of breast cancer. , 2007, The New England journal of medicine.

[61]  Lina Arbash Meinel,et al.  Breast MRI lesion classification: Improved performance of human readers with a backpropagation neural network computer‐aided diagnosis (CAD) system , 2007, Journal of magnetic resonance imaging : JMRI.

[62]  Mariko Goto,et al.  Diagnosis of breast tumors by contrast‐enhanced MR imaging: Comparison between the diagnostic performance of dynamic enhancement patterns and morphologic features , 2007, Journal of magnetic resonance imaging : JMRI.

[63]  F. Schmidt,et al.  Magnetic resonance imaging (MRI) of the breast , 1997, Acta Chirurgica Austriaca.

[64]  後藤 眞理子 Diagnosis of breast tumors by contrast-enhanced MR imaging : comparison between the diagnostic performance of dynamic enhancement patterns and morphologic features , 2007 .

[65]  J. Weidhaas,et al.  Locoregional relapse and distant metastasis in conservatively managed triple negative early-stage breast cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[66]  Daniel B Kopans,et al.  Physiologic Changes in Breast Magnetic Resonance Imaging during the Menstrual Cycle: Perfusion Imaging, Signal Enhancement, and Influence of the T1 Relaxation Time of Breast Tissue , 2005, The breast journal.

[67]  Kenneth G A Gilhuijs,et al.  Clinically and mammographically occult breast lesions on MR images: potential effect of computerized assessment on clinical reading. , 2005, Radiology.

[68]  C. Klifa,et al.  Quantification of breast tissue index from MR data using fuzzy clustering , 2004, The 26th Annual International Conference of the IEEE Engineering in Medicine and Biology Society.

[69]  Mina J Bissell,et al.  The organizing principle: microenvironmental influences in the normal and malignant breast. , 2002, Differentiation; research in biological diversity.

[70]  L. Liberman,et al.  Breast imaging reporting and data system (BI-RADS). , 2002, Radiologic clinics of North America.

[71]  P. Porter,et al.  Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. , 2000, Journal of the National Cancer Institute.

[72]  John C. Platt,et al.  Fast training of support vector machines using sequential minimal optimization, advances in kernel methods , 1999 .

[73]  C. Claussen,et al.  Menstrual cycle and age: influence on parenchymal contrast medium enhancement in MR imaging of the breast. , 1997, Radiology.

[74]  G Lutterbey,et al.  Healthy premenopausal breast parenchyma in dynamic contrast-enhanced MR imaging of the breast: normal contrast medium enhancement and cyclical-phase dependency. , 1997, Radiology.

[75]  Huan Liu,et al.  Chi2: feature selection and discretization of numeric attributes , 1995, Proceedings of 7th IEEE International Conference on Tools with Artificial Intelligence.

[76]  Ron Kohavi,et al.  A Study of Cross-Validation and Bootstrap for Accuracy Estimation and Model Selection , 1995, IJCAI.

[77]  Judea Pearl,et al.  Heuristics : intelligent search strategies for computer problem solving , 1984 .

[78]  Robert M. Haralick,et al.  Textural Features for Image Classification , 1973, IEEE Trans. Syst. Man Cybern..

[79]  E T BELL,et al.  The Diseases of the Breast , 1925, Nature.