Journal Article
. 2020 Oct;12(10).
doi: 10.3390/cancers12102772.

Integrated Multiparametric Radiomics and Informatics System for Characterizing Breast Tumor Characteristics with the OncotypeDX Gene Assay

Michael A Jacobs 1 Christopher B Umbricht 2 Vishwa S Parekh 1 Riham H El Khouli 3 Leslie Cope 4 Katarzyna J Macura 1 Susan Harvey 1 Antonio C Wolff 2 
  • PMID: 32992569
  •     54 References


Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained using the mpMRI, clinical, pathologic, and radiomic descriptors for prediction of the OncotypeDX risk score. The trained mpRad IRIS model had a 95% and specificity was 83% with an Area Under the Curve (AUC) of 0.89 for classifying low risk patients from the intermediate and high-risk groups. The lesion size was larger for the high-risk group (2.9 ± 1.7 mm) and lower for both low risk (1.9 ± 1.3 mm) and intermediate risk (1.7 ± 1.4 mm) groups. The lesion apparent diffusion coefficient (ADC) map values for high- and intermediate-risk groups were significantly (p < 0.05) lower than the low-risk group (1.14 vs. 1.49 × 10-3 mm2/s). These initial studies provide deeper insight into the clinical, pathological, quantitative imaging, and radiomic features, and provide the foundation to relate these features to the assessment of treatment response for improved personalized medicine.

Keywords: ADC map; DWI; IRIS; OncotypeDX; breast; cancer; diffusion-weighted imaging; informatics; machine learning; magnetic resonance imaging; mpRad; multiparametric radiomics; radiomics.

Dynamic contrast-enhanced MRI of the breast: quantitative method for kinetic curve type assessment.
Riham H El Khouli, Katarzyna J Macura, +4 authors, David A Bluemke.
AJR Am J Roentgenol, 2009 Sep 23; 193(4). PMID: 19770298    Free PMC article.
American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.
Lyndsay Harris, Herbert Fritsche, +7 authors, American Society of Clinical Oncology.
J Clin Oncol, 2007 Oct 24; 25(33). PMID: 17954709
Highly Cited. Review.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Texture analysis of medical images.
G Castellano, L Bonilha, L M Li, F Cendes.
Clin Radiol, 2004 Nov 24; 59(12). PMID: 15556588
Highly Cited. Review.
Prospective Validation of a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +28 authors, George W Sledge.
N Engl J Med, 2015 Sep 29; 373(21). PMID: 26412349    Free PMC article.
Highly Cited.
Magnetic resonance imaging in breast cancer.
M Van Goethem, W Tjalma, +3 authors, P Parizel.
Eur J Surg Oncol, 2006 Aug 22; 32(9). PMID: 16920327
Deep learning and radiomics in precision medicine.
Vishwa S Parekh, Michael A Jacobs.
Expert Rev Precis Med Drug Dev, 2019 May 14; 4(2). PMID: 31080889    Free PMC article.
CT-based radiomic signature predicts distant metastasis in lung adenocarcinoma.
Thibaud P Coroller, Patrick Grossmann, +7 authors, Hugo J W L Aerts.
Radiother Oncol, 2015 Mar 10; 114(3). PMID: 25746350    Free PMC article.
Highly Cited.
Multiparametric MR Imaging of Breast Cancer.
Habib Rahbar, Savannah C Partridge.
Magn Reson Imaging Clin N Am, 2015 Nov 29; 24(1). PMID: 26613883    Free PMC article.
Comparative analysis of nonlinear dimensionality reduction techniques for breast MRI segmentation.
Alireza Akhbardeh, Michael A Jacobs.
Med Phys, 2012 Apr 10; 39(4). PMID: 22482648    Free PMC article.
Separation of diffusion and perfusion in intravoxel incoherent motion MR imaging.
D Le Bihan, E Breton, +3 authors, M Laval-Jeantet.
Radiology, 1988 Aug 01; 168(2). PMID: 3393671
Highly Cited.
Development and evaluation of therapeutically relevant predictive classifiers using gene expression profiling.
Richard Simon.
J Natl Cancer Inst, 2006 Sep 07; 98(17). PMID: 16954463
A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.
Soonmyung Paik, Steven Shak, +12 authors, Norman Wolmark.
N Engl J Med, 2004 Dec 14; 351(27). PMID: 15591335
Highly Cited.
Relationship of temporal resolution to diagnostic performance for dynamic contrast enhanced MRI of the breast.
Riham H El Khouli, Katarzyna J Macura, +3 authors, David A Bluemke.
J Magn Reson Imaging, 2009 Oct 27; 30(5). PMID: 19856413    Free PMC article.
Breast Cancers Detected at Screening MR Imaging and Mammography in Patients at High Risk: Method of Detection Reflects Tumor Histopathologic Results.
Janice S Sung, Sarah Stamler, +6 authors, Christopher E Comstock.
Radiology, 2016 Apr 21; 280(3). PMID: 27097237    Free PMC article.
Collective dynamics of 'small-world' networks.
D J Watts, S H Strogatz.
Nature, 1998 Jun 12; 393(6684). PMID: 9623998
Highly Cited.
The effects of applying breast compression in dynamic contrast material-enhanced MR imaging.
Riham H El Khouli, Katarzyna J Macura, +2 authors, Michael A Jacobs.
Radiology, 2014 Mar 14; 272(1). PMID: 24620911    Free PMC article.
Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer.
Hyun-Seok Kim, Christopher B Umbricht, +22 authors, Leslie Cope.
J Clin Oncol, 2016 Dec 22; 34(36). PMID: 27998227    Free PMC article.
MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders.
D Le Bihan, E Breton, +3 authors, M Laval-Jeantet.
Radiology, 1986 Nov 01; 161(2). PMID: 3763909
Highly Cited.
Improved diagnostic accuracy of breast MRI through combined apparent diffusion coefficients and dynamic contrast-enhanced kinetics.
S C Partridge, H Rahbar, +4 authors, C D Lehman.
Magn Reson Med, 2011 Jan 22; 65(6). PMID: 21254208    Free PMC article.
A study of association of Oncotype DX recurrence score with DCE-MRI characteristics using multivariate machine learning models.
Ashirbani Saha, Michael R Harowicz, Weiyao Wang, Maciej A Mazurowski.
J Cancer Res Clin Oncol, 2018 Feb 11; 144(5). PMID: 29427210    Free PMC article.
Magnetic resonance imaging of the breast prior to biopsy.
David A Bluemke, Constantine A Gatsonis, +14 authors, Mitchell D Schnall.
JAMA, 2004 Dec 09; 292(22). PMID: 15585733
Highly Cited.
Characterization of soft tissue masses: can quantitative diffusion weighted imaging reliably distinguish cysts from solid masses?
Ty K Subhawong, Daniel J Durand, +2 authors, Laura M Fayad.
Skeletal Radiol, 2013 Aug 27; 42(11). PMID: 23974467
A global geometric framework for nonlinear dimensionality reduction.
J B Tenenbaum, V de Silva, J C Langford.
Science, 2000 Dec 23; 290(5500). PMID: 11125149
Highly Cited.
Magnetic resonance imaging of the breast.
Riham H El Khouli, Michael A Jacobs, David A Bluemke.
Semin Roentgenol, 2008 Sep 09; 43(4). PMID: 18774031
Measurement of pharmacokinetic parameters in histologically graded invasive breast tumours using dynamic contrast-enhanced MRI.
A Radjenovic, B J Dall, J P Ridgway, M A Smith.
Br J Radiol, 2007 Dec 12; 81(962). PMID: 18070824
3-T dynamic contrast-enhanced MRI of the breast: pharmacokinetic parameters versus conventional kinetic curve analysis.
Riham H El Khouli, Katarzyna J Macura, +2 authors, David A Bluemke.
AJR Am J Roentgenol, 2011 Nov 24; 197(6). PMID: 22109308    Free PMC article.
Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer.
P M Ravdin, L A Siminoff, +4 authors, H L Parker.
J Clin Oncol, 2001 Feb 22; 19(4). PMID: 11181660
Highly Cited.
Contrast-enhanced MRI for breast cancer screening.
Ritse M Mann, Christiane K Kuhl, Linda Moy.
J Magn Reson Imaging, 2019 Jan 20; 50(2). PMID: 30659696    Free PMC article.
Radiomics: a new application from established techniques.
Vishwa Parekh, Michael A Jacobs.
Expert Rev Precis Med Drug Dev, 2017 Jan 04; 1(2). PMID: 28042608    Free PMC article.
Highly Cited.
Use of archived specimens in evaluation of prognostic and predictive biomarkers.
Richard M Simon, Soonmyung Paik, Daniel F Hayes.
J Natl Cancer Inst, 2009 Oct 10; 101(21). PMID: 19815849    Free PMC article.
Highly Cited.
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917    Free PMC article.
Highly Cited.
Diffusion-weighted imaging improves the diagnostic accuracy of conventional 3.0-T breast MR imaging.
Riham H Ei Khouli, Michael A Jacobs, +4 authors, David A Bluemke.
Radiology, 2010 Jun 25; 256(1). PMID: 20574085    Free PMC article.
Highly Cited.
Diffusion magnetic resonance imaging: an early surrogate marker of therapeutic efficacy in brain tumors.
T L Chenevert, L D Stegman, +4 authors, B D Ross.
J Natl Cancer Inst, 2000 Dec 21; 92(24). PMID: 11121466
Highly Cited.
Dynamic field-of-view imaging to increase temporal resolution in the early phase of contrast media uptake in breast DCE-MRI: A feasibility study.
Federico D Pineda, Ty O Easley, Gregory S Karczmar.
Med Phys, 2018 Jan 10; 45(3). PMID: 29314060    Free PMC article.
Characterization of breast cancer types by texture analysis of magnetic resonance images.
Kirsi Holli, Anna-Leena Lääperi, +6 authors, Hannu Eskola.
Acad Radiol, 2009 Dec 01; 17(2). PMID: 19945302
Pharmacokinetic parameters in CNS Gd-DTPA enhanced MR imaging.
G Brix, W Semmler, +3 authors, W J Lorenz.
J Comput Assist Tomogr, 1991 Jul 01; 15(4). PMID: 2061479
Highly Cited.
Apparent diffusion coefficient in estrogen receptor-positive and lymph node-negative invasive breast cancers at 3.0T DW-MRI: A potential predictor for an oncotype Dx test recurrence score.
Sunitha B Thakur, Manuela Durando, +5 authors, Elizabeth A Morris.
J Magn Reson Imaging, 2017 Jun 24; 47(2). PMID: 28640531    Free PMC article.
Computer-aided diagnosis of breast DCE-MRI using pharmacokinetic model and 3-D morphology analysis.
Teh-Chen Wang, Yan-Hao Huang, +4 authors, Ruey-Feng Chang.
Magn Reson Imaging, 2014 Jan 21; 32(3). PMID: 24439361
Breast cancer. Clinical practice guidelines in oncology.
Robert W Carlson, D Craig Allred, +26 authors, NCCN Breast Cancer Clinical Practice Guidelines Panel.
J Natl Compr Canc Netw, 2009 Feb 10; 7(2). PMID: 19200416
Highly Cited. Review.
Emergence of scaling in random networks
Barabasi, Albert.
Science, 1999 Oct 16; 286(5439). PMID: 10521342
Highly Cited.
Radiomics: extracting more information from medical images using advanced feature analysis.
Philippe Lambin, Emmanuel Rios-Velazquez, +8 authors, Hugo J W L Aerts.
Eur J Cancer, 2012 Jan 20; 48(4). PMID: 22257792    Free PMC article.
Highly Cited. Review.
Measurement of the blood-brain barrier permeability and leakage space using dynamic MR imaging. 1. Fundamental concepts.
P S Tofts, A G Kermode.
Magn Reson Med, 1991 Feb 01; 17(2). PMID: 2062210
Highly Cited.
Multiparametric radiomics methods for breast cancer tissue characterization using radiological imaging.
Vishwa S Parekh, Michael A Jacobs.
Breast Cancer Res Treat, 2020 Feb 06; 180(2). PMID: 32020435    Free PMC article.
Breast cancer subtype intertumor heterogeneity: MRI-based features predict results of a genomic assay.
Elizabeth J Sutton, Jung Hun Oh, +5 authors, Elizabeth A Morris.
J Magn Reson Imaging, 2015 Apr 09; 42(5). PMID: 25850931    Free PMC article.
Highly Cited.
Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2019 Jun 04; 380(25). PMID: 31157962    Free PMC article.
Highly Cited.
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.
Hui Li, Yitan Zhu, +13 authors, Maryellen L Giger.
Radiology, 2016 Oct 19; 281(2). PMID: 27144536    Free PMC article.
Highly Cited.
Thresholds for therapies: highlights of the St Gallen International Expert Consensus on the primary therapy of early breast cancer 2009.
A Goldhirsch, J N Ingle, +4 authors, Panel members.
Ann Oncol, 2009 Jun 19; 20(8). PMID: 19535820    Free PMC article.
Highly Cited.
Textural analysis of contrast-enhanced MR images of the breast.
Peter Gibbs, Lindsay W Turnbull.
Magn Reson Med, 2003 Jun 20; 50(1). PMID: 12815683
Risk stratification of ER-positive breast cancer patients: A multi-institutional validation and outcome study of the Rochester Modified Magee algorithm (RoMMa) and prediction of an Oncotype DX® recurrence score <26.
Bradley M Turner, Mary Ann Gimenez-Sanders, +6 authors, David G Hicks.
Cancer Med, 2019 Jun 15; 8(9). PMID: 31199586    Free PMC article.
Multiparametric and Multimodality Functional Radiological Imaging for Breast Cancer Diagnosis and Early Treatment Response Assessment.
Michael A Jacobs, Antonio C Wolff, +5 authors, Richard Wahl.
J Natl Cancer Inst Monogr, 2015 Jun 13; 2015(51). PMID: 26063885    Free PMC article.
Impact of the 21-gene recurrence score assay compared with standard clinicopathologic guidelines in adjuvant therapy selection for node-negative, estrogen receptor-positive breast cancer.
Jessica F Partin, Eleftherios P Mamounas.
Ann Surg Oncol, 2011 May 04; 18(12). PMID: 21537874
Development, standardization, and testing of a lexicon for reporting contrast-enhanced breast magnetic resonance imaging studies.
D M Ikeda, N M Hylton, +9 authors, M D Schnall.
J Magn Reson Imaging, 2001 May 31; 13(6). PMID: 11382949
Integrated radiomic framework for breast cancer and tumor biology using advanced machine learning and multiparametric MRI.
Vishwa S Parekh, Michael A Jacobs.
NPJ Breast Cancer, 2017 Nov 21; 3. PMID: 29152563    Free PMC article.