Skip to main content
Erschienen in: Journal of Digital Imaging 2/2019

31.01.2019

Predicting Breast Cancer Molecular Subtype with MRI Dataset Utilizing Convolutional Neural Network Algorithm

verfasst von: Richard Ha, Simukayi Mutasa, Jenika Karcich, Nishant Gupta, Eduardo Pascual Van Sant, John Nemer, Mary Sun, Peter Chang, Michael Z. Liu, Sachin Jambawalikar

Erschienen in: Journal of Imaging Informatics in Medicine | Ausgabe 2/2019

Einloggen, um Zugang zu erhalten

Abstract

To develop a convolutional neural network (CNN) algorithm that can predict the molecular subtype of a breast cancer based on MRI features. An IRB-approved study was performed in 216 patients with available pre-treatment MRIs and immunohistochemical staining pathology data. First post-contrast MRI images were used for 3D segmentation using 3D slicer. A CNN architecture was designed with 14 layers. Residual connections were used in the earlier layers to allow stabilization of gradients during backpropagation. Inception style layers were utilized deeper in the network to allow learned segregation of more complex feature mappings. Extensive regularization was utilized including dropout, L2, feature map dropout, and transition layers. The class imbalance was addressed by doubling the input of underrepresented classes and utilizing a class sensitive cost function. Parameters were tuned based on a 20% validation group. A class balanced holdout set of 40 patients was utilized as the testing set. Software code was written in Python using the TensorFlow module on a Linux workstation with one NVidia Titan X GPU. Seventy-four luminal A, 106 luminal B, 13 HER2+, and 23 basal breast tumors were evaluated. Testing set accuracy was measured at 70%. The class normalized macro area under receiver operating curve (ROC) was measured at 0.853. Non-normalized micro-aggregated AUC was measured at 0.871, representing improved discriminatory power for the highly represented Luminal A and Luminal B subtypes. Aggregate sensitivity and specificity was measured at 0.603 and 0.958. MRI analysis of breast cancers utilizing a novel CNN can predict the molecular subtype of breast cancers. Larger data sets will likely improve our model.
Literatur
1.
2.
Zurück zum Zitat Perou CM, Sørlie T, Eisen MB et al.: Molecular portraits of human breast tumours. Nature 406(6797):747–752, 2000CrossRefPubMed Perou CM, Sørlie T, Eisen MB et al.: Molecular portraits of human breast tumours. Nature 406(6797):747–752, 2000CrossRefPubMed
3.
Zurück zum Zitat Morris EA: Diagnostic breast MR imaging: current status and future directions. Magn Reson Imaging Clin N Am 18:57–74, 2010CrossRefPubMed Morris EA: Diagnostic breast MR imaging: current status and future directions. Magn Reson Imaging Clin N Am 18:57–74, 2010CrossRefPubMed
4.
Zurück zum Zitat Liberman L, Morris EA, Dershaw DD et al.: MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol 180(4):901–910, 2003CrossRefPubMed Liberman L, Morris EA, Dershaw DD et al.: MR imaging of the ipsilateral breast in women with percutaneously proven breast cancer. AJR Am J Roentgenol 180(4):901–910, 2003CrossRefPubMed
5.
Zurück zum Zitat Schelfout K, Van Goethem M, Kersschot E et al.: Contrast-enhanced MR imaging of breast lesions and effect on treatment. Eur J Surg Oncol. 30(5):501–507, 2004CrossRefPubMed Schelfout K, Van Goethem M, Kersschot E et al.: Contrast-enhanced MR imaging of breast lesions and effect on treatment. Eur J Surg Oncol. 30(5):501–507, 2004CrossRefPubMed
6.
Zurück zum Zitat Sørlie T, Perou CM, Tibshirani R et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874, 2001CrossRefPubMedPubMedCentral Sørlie T, Perou CM, Tibshirani R et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874, 2001CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Wiechmann L, Sampson M, Stempel M et al.: Presenting features of breast cancer differ by molecular subtype. Ann Surg Oncol 16(10):2705–2710, 2009CrossRefPubMed Wiechmann L, Sampson M, Stempel M et al.: Presenting features of breast cancer differ by molecular subtype. Ann Surg Oncol 16(10):2705–2710, 2009CrossRefPubMed
8.
Zurück zum Zitat Morrow M, Waters J, Morris E: MRI for breast cancer screening, diagnosis, and treatment. Lancet 378:1804–1811, 2011CrossRefPubMed Morrow M, Waters J, Morris E: MRI for breast cancer screening, diagnosis, and treatment. Lancet 378:1804–1811, 2011CrossRefPubMed
9.
Zurück zum Zitat Goldhirsch A, Wood WC, Coates AS et al.: Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747, 2011CrossRefPubMedPubMedCentral Goldhirsch A, Wood WC, Coates AS et al.: Strategies for subtypes--dealing with the diversity of breast cancer: highlights of the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. Ann Oncol 22(8):1736–1747, 2011CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Metzger-Filho O, Sun Z, Viale G et al.: Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international Breast Cancer Study Group Trials VIII and IX. J Clin Oncol 31(25):3083–3090, 2013CrossRefPubMedPubMedCentral Metzger-Filho O, Sun Z, Viale G et al.: Patterns of recurrence and outcome according to breast cancer subtypes in lymph node-negative disease: results from international Breast Cancer Study Group Trials VIII and IX. J Clin Oncol 31(25):3083–3090, 2013CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F et al.: The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334, 2007CrossRefPubMed Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F et al.: The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res 13(8):2329–2334, 2007CrossRefPubMed
12.
Zurück zum Zitat Kumar V, Gu Y, Basu S, Berglund A, Eschrich SA, Schabath MB et al.: Radiomics: the process and the challenges. Magn Reson Imaging 30(9):1234–1248, 2012CrossRefPubMedPubMedCentral Kumar V, Gu Y, Basu S, Berglund A, Eschrich SA, Schabath MB et al.: Radiomics: the process and the challenges. Magn Reson Imaging 30(9):1234–1248, 2012CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Kuo MD, Jamshidi N: Behind the numbers: Decoding molecular phenotypes with radiogenomics—guiding principles and technical considerations. Radiology 270(2):320–325, 2014CrossRefPubMed Kuo MD, Jamshidi N: Behind the numbers: Decoding molecular phenotypes with radiogenomics—guiding principles and technical considerations. Radiology 270(2):320–325, 2014CrossRefPubMed
14.
Zurück zum Zitat Holli-Helenius K, Salminen A, Rinta-Kiikka I et al.: MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study. BMC Med Imaging 17(1):69, 2017CrossRefPubMedPubMedCentral Holli-Helenius K, Salminen A, Rinta-Kiikka I et al.: MRI texture analysis in differentiating luminal A and luminal B breast cancer molecular subtypes - a feasibility study. BMC Med Imaging 17(1):69, 2017CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat Chen W, Giger ML, Lan L, Bick U: Computerized interpretation of breast MRI: investigation of enhancement-variance dynamics. Med Phys 31:1076–1108, 2004CrossRefPubMed Chen W, Giger ML, Lan L, Bick U: Computerized interpretation of breast MRI: investigation of enhancement-variance dynamics. Med Phys 31:1076–1108, 2004CrossRefPubMed
16.
Zurück zum Zitat Guo W, Li H, Zhu Y et al.: Prediction of clinical phenotypes in invasive breast carcinomas from the integration of radiomics and genomics data. J Med Imaging (Bellingham) 2:041007, 2015CrossRef Guo W, Li H, Zhu Y et al.: Prediction of clinical phenotypes in invasive breast carcinomas from the integration of radiomics and genomics data. J Med Imaging (Bellingham) 2:041007, 2015CrossRef
17.
Zurück zum Zitat Fan M, Li H, Wang S et al.: Radiomic analysis reveals DCE-MRI features for prediction of molecular subtypes of breast cancer. PLoS One 12(2):e0171683, 2017CrossRefPubMedPubMedCentral Fan M, Li H, Wang S et al.: Radiomic analysis reveals DCE-MRI features for prediction of molecular subtypes of breast cancer. PLoS One 12(2):e0171683, 2017CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat Bhooshan N, Giger ML, Jansen SA et al.: Cancerous breast lesions on dynamic contrast-enhanced MR images: computerized characterization for image-based prognostic markers. Radiology. 254(3):680–690, 2010CrossRefPubMedPubMedCentral Bhooshan N, Giger ML, Jansen SA et al.: Cancerous breast lesions on dynamic contrast-enhanced MR images: computerized characterization for image-based prognostic markers. Radiology. 254(3):680–690, 2010CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Bhooshan N, Giger M, Edwards D et al.: Computerized three-class classification of MRI-based prognostic markers for breast cancer. Phys Med Biol 56(18):5995–6008, 2011CrossRefPubMedPubMedCentral Bhooshan N, Giger M, Edwards D et al.: Computerized three-class classification of MRI-based prognostic markers for breast cancer. Phys Med Biol 56(18):5995–6008, 2011CrossRefPubMedPubMedCentral
20.
Zurück zum Zitat Agner SC, Rosen MA, Englander S 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. Radiology 272:91–99, 2014CrossRefPubMed Agner SC, Rosen MA, Englander S 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. Radiology 272:91–99, 2014CrossRefPubMed
21.
Zurück zum Zitat Mazurowski MA, Zhang J, Grimm LJ et al.: Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging. Radiology 273(2):365–372, 2014CrossRefPubMed Mazurowski MA, Zhang J, Grimm LJ et al.: Radiogenomic analysis of breast cancer: luminal B molecular subtype is associated with enhancement dynamics at MR imaging. Radiology 273(2):365–372, 2014CrossRefPubMed
22.
Zurück zum Zitat Grimm LJ, Zhang J, Mazurowski MA: 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. J Magn Reson Imaging 42(4):902–907, 2015CrossRefPubMed Grimm LJ, Zhang J, Mazurowski MA: 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. J Magn Reson Imaging 42(4):902–907, 2015CrossRefPubMed
23.
Zurück zum Zitat Yamamoto S, Han W, Kim Y et al.: Breast cancer: radiogenomic biomarker reveals associations among dynamic contrast-enhanced MR imaging, long noncoding RNA, and metastasis. Radiology 275(2):384–392, 2015CrossRefPubMed Yamamoto S, Han W, Kim Y et al.: Breast cancer: radiogenomic biomarker reveals associations among dynamic contrast-enhanced MR imaging, long noncoding RNA, and metastasis. Radiology 275(2):384–392, 2015CrossRefPubMed
24.
Zurück zum Zitat Ashraf AB, Daye D, Gavenonis S et al.: Identification of intrinsic imaging phenotypes for breast cancer tumors: preliminary associations with gene expression profiles. Radiology 272(2):374–384, 2014CrossRefPubMed Ashraf AB, Daye D, Gavenonis S et al.: Identification of intrinsic imaging phenotypes for breast cancer tumors: preliminary associations with gene expression profiles. Radiology 272(2):374–384, 2014CrossRefPubMed
25.
Zurück zum Zitat Yamaguchi K, Abe H, Newstread G et al.: Intratumoral heterogeneity of the distribution of kinetic parameters in breast cancer: comparison based on the molecular subtypes of invasive breast cancer. Breast Cancer 22(5):496–502, 2015CrossRefPubMed Yamaguchi K, Abe H, Newstread G et al.: Intratumoral heterogeneity of the distribution of kinetic parameters in breast cancer: comparison based on the molecular subtypes of invasive breast cancer. Breast Cancer 22(5):496–502, 2015CrossRefPubMed
26.
Zurück zum Zitat Blaschke E, Abe H: MRI phenotype of breast cancer: kinetic assessment for molecular subtypes. J Magn Reson Imaging 42(4):920–924, 2015CrossRefPubMed Blaschke E, Abe H: MRI phenotype of breast cancer: kinetic assessment for molecular subtypes. J Magn Reson Imaging 42(4):920–924, 2015CrossRefPubMed
27.
Zurück zum Zitat LeChun Y, Bengio T, Hinton G: Deep learning. Nature 521:436–444, 2015CrossRef LeChun Y, Bengio T, Hinton G: Deep learning. Nature 521:436–444, 2015CrossRef
28.
Zurück zum Zitat Ha R, Jin B, Mango V et al.: Breast cancer molecular subtype as a predictor of the utility of preoperative MRI. AJR Am J Roentgenol 204(6):1354–1360, 2015CrossRefPubMed Ha R, Jin B, Mango V et al.: Breast cancer molecular subtype as a predictor of the utility of preoperative MRI. AJR Am J Roentgenol 204(6):1354–1360, 2015CrossRefPubMed
29.
Zurück zum Zitat Carey LA, Perou CM, Livasy CA et al.: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502, 2006CrossRefPubMed Carey LA, Perou CM, Livasy CA et al.: Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295:2492–2502, 2006CrossRefPubMed
30.
Zurück zum Zitat Nguyen PL, Taghian AG, Katz MS 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. J Clin Oncol 26(14):2373–2828, 2008CrossRefPubMed Nguyen PL, Taghian AG, Katz MS 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. J Clin Oncol 26(14):2373–2828, 2008CrossRefPubMed
31.
Zurück zum Zitat LeCun Y, Bottou L, Bengio Y et al.: Gradient-based learning applied to document recognition. Proceed IEEE 86(11):2278–2324, 1998CrossRef LeCun Y, Bottou L, Bengio Y et al.: Gradient-based learning applied to document recognition. Proceed IEEE 86(11):2278–2324, 1998CrossRef
32.
Zurück zum Zitat He K, Zhang X, Ren S, et al: Deep residual learning for image recognition. In: Proceedings of the IEEE conference on computer vision and pattern recognition, 2016, pp 770–778 He K, Zhang X, Ren S, et al: Deep residual learning for image recognition. In: Proceedings of the IEEE conference on computer vision and pattern recognition, 2016, pp 770–778
33.
Zurück zum Zitat Nair, V, Hinton GE: Rectified linear units improve restricted boltzmann machines. In: Proceedings of the 27th international conference on machine learning (ICML-10), 2010, pp 807–814 Nair, V, Hinton GE: Rectified linear units improve restricted boltzmann machines. In: Proceedings of the 27th international conference on machine learning (ICML-10), 2010, pp 807–814
34.
Zurück zum Zitat Ioffe S, Szegedy C: Batch normalization: accelerating deep network training by reducing internal covariate shift. In: International Conference on Machine Learning, 2015 Ioffe S, Szegedy C: Batch normalization: accelerating deep network training by reducing internal covariate shift. In: International Conference on Machine Learning, 2015
35.
Zurück zum Zitat Srivastava N, Hinton G, Krizhevsky A et al.: Dropout: a simple way to prevent neural networks from overfitting. J Mach Learn Res 15(1):1929–1958, 2014 Srivastava N, Hinton G, Krizhevsky A et al.: Dropout: a simple way to prevent neural networks from overfitting. J Mach Learn Res 15(1):1929–1958, 2014
36.
Zurück zum Zitat Kingma DP, Jimmy BA: Adam: a method for stochastic optimization. arXiv preprint arXiv:1412.6980. 2014 Kingma DP, Jimmy BA: Adam: a method for stochastic optimization. arXiv preprint arXiv:1412.6980. 2014
37.
Zurück zum Zitat Nesterov Y: Gradient methods for minimizing composite objective function. 2007 Nesterov Y: Gradient methods for minimizing composite objective function. 2007
38.
Zurück zum Zitat Dozat T: Incorporating nesterov momentum into adam. 2016 Dozat T: Incorporating nesterov momentum into adam. 2016
39.
Zurück zum Zitat Glorot X, Bengio Y: Understanding the difficulty of training deep feedforward neural networks. In: Proceedings of the thirteenth international conference on artificial intelligence and statistics, 2010, pp 249–256 Glorot X, Bengio Y: Understanding the difficulty of training deep feedforward neural networks. In: Proceedings of the thirteenth international conference on artificial intelligence and statistics, 2010, pp 249–256
40.
Zurück zum Zitat Zhu Z, Albadawy E, Saha A, et al: Breast cancer molecular subtype classification using deep features: preliminary results. In: Proceedings Volume 10575, Medical imaging 2018: computer-aided diagnosis; 105752X. 2018 Zhu Z, Albadawy E, Saha A, et al: Breast cancer molecular subtype classification using deep features: preliminary results. In: Proceedings Volume 10575, Medical imaging 2018: computer-aided diagnosis; 105752X. 2018
41.
Zurück zum Zitat Sun C, Shrivastaval A, Singh S, et al: Revisiting unreasonable effectiveness of data in deep learning Era. arXiv preprint arXIV:1707.02968. 2017 Sun C, Shrivastaval A, Singh S, et al: Revisiting unreasonable effectiveness of data in deep learning Era. arXiv preprint arXIV:1707.02968. 2017
42.
Zurück zum Zitat Guiu S, Michiels S, André F et al.: Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 Working Group Statement. Ann Oncol 23(12):2997–3006, 2012CrossRefPubMed Guiu S, Michiels S, André F et al.: Molecular subclasses of breast cancer: how do we define them? The IMPAKT 2012 Working Group Statement. Ann Oncol 23(12):2997–3006, 2012CrossRefPubMed
Metadaten
Titel
Predicting Breast Cancer Molecular Subtype with MRI Dataset Utilizing Convolutional Neural Network Algorithm
verfasst von
Richard Ha
Simukayi Mutasa
Jenika Karcich
Nishant Gupta
Eduardo Pascual Van Sant
John Nemer
Mary Sun
Peter Chang
Michael Z. Liu
Sachin Jambawalikar
Publikationsdatum
31.01.2019
Verlag
Springer International Publishing
Erschienen in
Journal of Imaging Informatics in Medicine / Ausgabe 2/2019
Print ISSN: 2948-2925
Elektronische ISSN: 2948-2933
DOI
https://doi.org/10.1007/s10278-019-00179-2

Weitere Artikel der Ausgabe 2/2019

Journal of Digital Imaging 2/2019 Zur Ausgabe

Update Radiologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.