Relationships Between Human-Extracted MRI Tumor Phenotypes of Breast Cancer and Clinical Prognostic Indicators Including Receptor Status and Molecular Subtype.

PURPOSE The purpose of this study was to investigate if human-extracted MRI tumor phenotypes of breast cancer could predict receptor status and tumor molecular subtype using MRIs from The Cancer Genome Atlas project. MATERIALS AND METHODS Our retrospective interpretation study utilized the analysis of HIPAA-compliant breast MRI data from The Cancer Imaging Archive. One hundred and seven preoperative breast MRIs of biopsy proven invasive breast cancers were analyzed by 3 fellowship-trained breast-imaging radiologists. Each study was scored according to the Breast Imaging Reporting and Data System lexicon for mass and nonmass features. The Spearman rank correlation was used for association analysis of continuous variables; the Kruskal-Wallis test was used for associating continuous outcomes with categorical variables. The Fisher-exact test was used to assess correlations between categorical image-derived features and receptor status. Prediction of estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor, and molecular subtype were performed using random forest classifiers. RESULTS ER+ tumors were associated with the absence of rim enhancement (P = 0.019, odds ratio [OR] 5.5), heterogeneous internal enhancement (P = 0.02, OR 6.5), peritumoral edema (P = 0.0001, OR 10.0), and axillary adenopathy (P = 0.04, OR 4.4). ER+ tumors were smaller than ER- tumors (23.7mm vs 29.2mm, P = 0.02, OR 8.2). All of these variables except the lack of axillary adenopathy were also associated with progesterone receptor+ status. Luminal A tumors (n = 57) were smaller compared to nonLuminal A (21.8mm vs 27.5mm, P = 0.035, OR 7.3) and lacked peritumoral edema (P = 0.001, OR 6.8). Basal like tumors were associated with heterogeneous internal enhancement (P = 0.05, OR 10.1), rim enhancement (P = 0.05, OR6.9), and perituomral edema (P = 0.0001, OR 13.8). CONCLUSIONS Human extracted MRI tumor phenotypes may be able to differentiate those tumors with a more favorable clinical prognosis from their more aggressive counterparts.

[1]  Steven Sourbron,et al.  Deconvolution-based dynamic contrast-enhanced MR imaging of breast tumors: correlation of tumor blood flow with human epidermal growth factor receptor 2 status and clinicopathologic findings--preliminary results. , 2008, Radiology.

[2]  R. Fisher On the Interpretation of χ2 from Contingency Tables, and the Calculation of P , 2010 .

[3]  A. Giuliano,et al.  Personalizing breast cancer staging by the inclusion of ER, PR, and HER2. , 2014, JAMA surgery.

[4]  Maryellen Giger,et al.  Computerized three-class classification of MRI-based prognostic markers for breast cancer , 2011, Physics in medicine and biology.

[5]  C. Perou,et al.  Genomics, prognosis, and therapeutic interventions , 2014 .

[6]  Leo Breiman,et al.  Random Forests , 2001, Machine Learning.

[7]  Lars J. Grimm,et al.  Computational approach to radiogenomics of breast cancer: Luminal A and luminal B molecular subtypes are associated with imaging features on routine breast MRI extracted using computer vision algorithms , 2015, Journal of magnetic resonance imaging : JMRI.

[8]  A. Nobel,et al.  Supervised risk predictor of breast cancer based on intrinsic subtypes. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[9]  E. Morris Diagnostic breast MR imaging: current status and future directions. , 2007, Radiologic clinics of North America.

[10]  Lorenzo Bonomo,et al.  Magnetic resonance imaging features in triple-negative breast cancer: comparison with luminal and HER2-overexpressing tumors. , 2012, Clinical breast cancer.

[11]  Neema Jamshidi,et al.  Breast Cancer: Radiogenomic Biomarker Reveals Associations among Dynamic Contrast-enhanced MR Imaging, Long Noncoding RNA, and Metastasis. , 2015, Radiology.

[12]  Stephen M. Moore,et al.  The Cancer Imaging Archive (TCIA): Maintaining and Operating a Public Information Repository , 2013, Journal of Digital Imaging.

[13]  Steven J. M. Jones,et al.  Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer , 2015, Cell.

[14]  R. Fisher 019: On the Interpretation of x2 from Contingency Tables, and the Calculation of P. , 1922 .

[15]  M. Noguchi,et al.  Two different types of ring‐like enhancement on dynamic MR imaging in breast cancer: Correlation with the histopathologic findings , 2008, Journal of magnetic resonance imaging : JMRI.

[16]  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.

[17]  Li Lan,et al.  Computerized assessment of breast lesion malignancy using DCE-MRI robustness study on two independent clinical datasets from two manufacturers. , 2010, Academic radiology.

[18]  L. Carey,et al.  Breast cancer molecular subtypes in patients with locally advanced disease: impact on prognosis, patterns of recurrence, and response to therapy. , 2009, Seminars in radiation oncology.

[19]  Erich P Huang,et al.  Quantitative MRI radiomics in the prediction of molecular classifications of breast cancer subtypes in the TCGA/TCIA data set , 2016, npj Breast Cancer.

[20]  A Horsman,et al.  Prediction of axillary lymph node status in invasive breast cancer with dynamic contrast-enhanced MR imaging. , 1997, Radiology.

[21]  S. Jeffrey,et al.  Estrogen receptor-negative invasive breast cancer: imaging features of tumors with and without human epidermal growth factor receptor type 2 overexpression. , 2008, Radiology.

[22]  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.

[23]  Monica Morrow,et al.  Presenting Features of Breast Cancer Differ by Molecular Subtype , 2009, Annals of Surgical Oncology.

[24]  Eric M Blaschke,et al.  MRI phenotype of breast cancer: Kinetic assessment for molecular subtypes , 2015, Journal of magnetic resonance imaging : JMRI.

[25]  Erich P Huang,et al.  Using computer‐extracted image phenotypes from tumors on breast magnetic resonance imaging to predict breast cancer pathologic stage , 2016, Cancer.

[26]  Erich P Huang,et al.  MR Imaging Radiomics Signatures for Predicting the Risk of Breast Cancer Recurrence as Given by Research Versions of MammaPrint, Oncotype DX, and PAM50 Gene Assays. , 2016, Radiology.

[27]  J. Pietenpol,et al.  Identification and use of biomarkers in treatment strategies for triple‐negative breast cancer subtypes , 2014, The Journal of pathology.

[28]  G. Newstead,et al.  Intratumoral heterogeneity of the distribution of kinetic parameters in breast cancer: comparison based on the molecular subtypes of invasive breast cancer , 2015, Breast Cancer.

[29]  Janet Waters,et al.  MRI for breast cancer screening, diagnosis, and treatment , 2011, The Lancet.

[30]  N. Graham,et al.  Areas beneath the relative operating characteristics (ROC) and relative operating levels (ROL) curves: Statistical significance and interpretation , 2002 .

[31]  W. Kruskal,et al.  Use of Ranks in One-Criterion Variance Analysis , 1952 .

[32]  H. Lehr,et al.  Dynamic MR imaging of breast lesions: correlation with microvessel distribution pattern and histologic characteristics of prognosis. , 2006, Radiology.

[33]  M. Giger,et al.  Volumetric texture analysis of breast lesions on contrast‐enhanced magnetic resonance images , 2007, Magnetic resonance in medicine.

[34]  Megumi Jinguji,et al.  Rim enhancement of breast cancers on contrast-enhanced MR imaging: Relationship with prognostic factors , 2006, Breast cancer.

[35]  Daniel L. Rubin,et al.  The National Cancer Informatics Program (NCIP) Annotation and Image Markup (AIM) Foundation Model , 2014, Journal of Digital Imaging.

[36]  Barbara L. Smith,et al.  Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[37]  Wei Tse Yang,et al.  Identification of Intrinsic Imaging Phenotypes for Breast Cancer Tumors: Preliminary Associations with Gene Expression Profiles , 2015 .

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

[39]  Daniel L. Rubin,et al.  Dynamic contrast-enhanced MRI-based biomarkers of therapeutic response in triple-negative breast cancer. , 2013, Journal of the American Medical Informatics Association : JAMIA.

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

[41]  Lars J. Grimm,et al.  Can breast cancer molecular subtype help to select patients for preoperative MR imaging? , 2015, Radiology.

[42]  Eun Sook Ko,et al.  Apparent diffusion coefficient in estrogen receptor-positive invasive ductal breast carcinoma: correlations with tumor-stroma ratio. , 2014, Radiology.

[43]  M. Giger,et al.  Automatic identification and classification of characteristic kinetic curves of breast lesions on DCE-MRI. , 2006, Medical physics.

[44]  D. D. Maki,et al.  Radiogenomic analysis of breast cancer using MRI: a preliminary study to define the landscape. , 2012, AJR. American journal of roentgenology.

[45]  M. Giger,et al.  Deciphering Genomic Underpinnings of Quantitative MRI-based Radiomic Phenotypes of Invasive Breast Carcinoma , 2015, Scientific Reports.

[46]  S. O'toole,et al.  Prediction of local recurrence, distant metastases, and death after breast-conserving therapy in early-stage invasive breast cancer using a five-biomarker panel. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[47]  M. Giger,et al.  Computerized interpretation of breast MRI: investigation of enhancement-variance dynamics. , 2004, Medical physics.

[48]  Ahmed Bilal Ashraf,et al.  Identification of intrinsic imaging phenotypes for breast cancer tumors: preliminary associations with gene expression profiles. , 2014, Radiology.

[49]  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.

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

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

[52]  Maryellen L. Giger,et al.  Prediction of clinical phenotypes in invasive breast carcinomas from the integration of radiomics and genomics data , 2015, Journal of medical imaging.

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

[54]  Y. Benjamini,et al.  Controlling the false discovery rate: a practical and powerful approach to multiple testing , 1995 .