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      Classification of breast cancer histology images using Convolutional Neural Networks

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          Abstract

          Breast cancer is one of the main causes of cancer death worldwide. The diagnosis of biopsy tissue with hematoxylin and eosin stained images is non-trivial and specialists often disagree on the final diagnosis. Computer-aided Diagnosis systems contribute to reduce the cost and increase the efficiency of this process. Conventional classification approaches rely on feature extraction methods designed for a specific problem based on field-knowledge. To overcome the many difficulties of the feature-based approaches, deep learning methods are becoming important alternatives. A method for the classification of hematoxylin and eosin stained breast biopsy images using Convolutional Neural Networks (CNNs) is proposed. Images are classified in four classes, normal tissue, benign lesion, in situ carcinoma and invasive carcinoma, and in two classes, carcinoma and non-carcinoma. The architecture of the network is designed to retrieve information at different scales, including both nuclei and overall tissue organization. This design allows the extension of the proposed system to whole-slide histology images. The features extracted by the CNN are also used for training a Support Vector Machine classifier. Accuracies of 77.8% for four class and 83.3% for carcinoma/non-carcinoma are achieved. The sensitivity of our method for cancer cases is 95.6%.

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          Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up.

          Morphological assessment of the degree of differentiation has been shown in numerous studies to provide useful prognostic information in breast cancer, but until recently histological grading has not been accepted as a routine procedure, mainly because of perceived problems with reproducibility and consistency. In the Nottingham/Tenovus Primary Breast Cancer Study the most commonly used method, described by Bloom & Richardson, has been modified in order to make the criteria more objective. The revised technique involves semiquantitative evaluation of three morphological features--the percentage of tubule formation, the degree of nuclear pleomorphism and an accurate mitotic count using a defined field area. A numerical scoring system is used and the overall grade is derived from a summation of individual scores for the three variables: three grades of differentiation are used. Since 1973, over 2200 patients with primary operable breast cancer have been entered into a study of multiple prognostic factors. Histological grade, assessed in 1831 patients, shows a very strong correlation with prognosis; patients with grade I tumours have a significantly better survival than those with grade II and III tumours (P less than 0.0001). These results demonstrate that this method for histological grading provides important prognostic information and, if the grading protocol is followed consistently, reproducible results can be obtained. Histological grade forms part of the multifactorial Nottingham prognostic index, together with tumour size and lymph node stage, which is used to stratify individual patients for appropriate therapy.
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            Deep learning as a tool for increased accuracy and efficiency of histopathological diagnosis

            Pathologists face a substantial increase in workload and complexity of histopathologic cancer diagnosis due to the advent of personalized medicine. Therefore, diagnostic protocols have to focus equally on efficiency and accuracy. In this paper we introduce ‘deep learning’ as a technique to improve the objectivity and efficiency of histopathologic slide analysis. Through two examples, prostate cancer identification in biopsy specimens and breast cancer metastasis detection in sentinel lymph nodes, we show the potential of this new methodology to reduce the workload for pathologists, while at the same time increasing objectivity of diagnoses. We found that all slides containing prostate cancer and micro- and macro-metastases of breast cancer could be identified automatically while 30–40% of the slides containing benign and normal tissue could be excluded without the use of any additional immunohistochemical markers or human intervention. We conclude that ‘deep learning’ holds great promise to improve the efficacy of prostate cancer diagnosis and breast cancer staging.
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              Diagnostic concordance among pathologists interpreting breast biopsy specimens.

              A breast pathology diagnosis provides the basis for clinical treatment and management decisions; however, its accuracy is inadequately understood. To quantify the magnitude of diagnostic disagreement among pathologists compared with a consensus panel reference diagnosis and to evaluate associated patient and pathologist characteristics. Study of pathologists who interpret breast biopsies in clinical practices in 8 US states. Participants independently interpreted slides between November 2011 and May 2014 from test sets of 60 breast biopsies (240 total cases, 1 slide per case), including 23 cases of invasive breast cancer, 73 ductal carcinoma in situ (DCIS), 72 with atypical hyperplasia (atypia), and 72 benign cases without atypia. Participants were blinded to the interpretations of other study pathologists and consensus panel members. Among the 3 consensus panel members, unanimous agreement of their independent diagnoses was 75%, and concordance with the consensus-derived reference diagnoses was 90.3%. The proportions of diagnoses overinterpreted and underinterpreted relative to the consensus-derived reference diagnoses were assessed. Sixty-five percent of invited, responding pathologists were eligible and consented to participate. Of these, 91% (N = 115) completed the study, providing 6900 individual case diagnoses. Compared with the consensus-derived reference diagnosis, the overall concordance rate of diagnostic interpretations of participating pathologists was 75.3% (95% CI, 73.4%-77.0%; 5194 of 6900 interpretations). Among invasive carcinoma cases (663 interpretations), 96% (95% CI, 94%-97%) were concordant, and 4% (95% CI, 3%-6%) were underinterpreted; among DCIS cases (2097 interpretations), 84% (95% CI, 82%-86%) were concordant, 3% (95% CI, 2%-4%) were overinterpreted, and 13% (95% CI, 12%-15%) were underinterpreted; among atypia cases (2070 interpretations), 48% (95% CI, 44%-52%) were concordant, 17% (95% CI, 15%-21%) were overinterpreted, and 35% (95% CI, 31%-39%) were underinterpreted; and among benign cases without atypia (2070 interpretations), 87% (95% CI, 85%-89%) were concordant and 13% (95% CI, 11%-15%) were overinterpreted. Disagreement with the reference diagnosis was statistically significantly higher among biopsies from women with higher (n = 122) vs lower (n = 118) breast density on prior mammograms (overall concordance rate, 73% [95% CI, 71%-75%] for higher vs 77% [95% CI, 75%-80%] for lower, P < .001), and among pathologists who interpreted lower weekly case volumes (P < .001) or worked in smaller practices (P = .034) or nonacademic settings (P = .007). In this study of pathologists, in which diagnostic interpretation was based on a single breast biopsy slide, overall agreement between the individual pathologists' interpretations and the expert consensus-derived reference diagnoses was 75.3%, with the highest level of concordance for invasive carcinoma and lower levels of concordance for DCIS and atypia. Further research is needed to understand the relationship of these findings with patient management.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2017
                1 June 2017
                : 12
                : 6
                : e0177544
                Affiliations
                [1 ]Faculdade de Engenharia da Universidade do Porto (FEUP), R. Dr. Roberto Frias s/n, 4200-465 Porto, Portugal
                [2 ]Instituto de Engenharia de Sistemas e Computadores - Tecnologia e Ciência (INESC-TEC), R. Dr. Roberto Frias, 4200 Porto, Portugal
                [3 ]Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
                [4 ]Instituto de Engenharia Biomédica (INEB), Universidade do Porto, Rua Alfredo Allen, 208, 4200-135 Porto, Portugal
                [5 ]Laboratório de Anatomia Patológica, Ipatimup Diagnósticos, Rua Júlio Amaral de Carvalho, 45, 4200-135 Porto, Portugal
                [6 ]Faculdade de Medicina, Universidade do Porto, Alameda Prof Hernâni Monteiro, 4200-319 Porto, Portugal
                Universita degli Studi di Torino, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Data curation: PA CE AP.

                • Methodology: TA GA EC JR.

                • Software: TA GA EC JR.

                • Supervision: AC.

                • Writing – original draft: TA GA EC JR.

                • Writing – review & editing: TA GA EC JR PA CE AP AC.

                Author information
                http://orcid.org/0000-0001-9687-528X
                Article
                PONE-D-16-48431
                10.1371/journal.pone.0177544
                5453426
                28570557
                63f33fbe-50ba-464e-bd40-6b025ad8fb35
                © 2017 Araújo et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 7 December 2016
                : 28 April 2017
                Page count
                Figures: 5, Tables: 6, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100001871, Fundação para a Ciência e a Tecnologia;
                Award ID: SFRH/BD/122365/2016
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001871, Fundação para a Ciência e a Tecnologia;
                Award ID: SFRH/BD/120435/2016
                Award Recipient :
                Funded by: Fundação para a Ciência e a Tecnologia (PT)
                Award ID: FRH/BPD/79154/2011
                Award Recipient :
                Funded by: North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF)
                Award ID: NanoSTIMA: Macro-to-Nano Human Sensing: Towards Integrated Multimodal Health Monitoring and Analytics/NORTE-01-0145-FEDER-000016
                Project "NanoSTIMA: Macro-to-Nano Human Sensing: Towards Integrated Multimodal Health Monitoring and Analytics/NORTE-01-0145-FEDER-000016" is financed by the North Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, and through the European Regional Development Fund (ERDF). Teresa Araújo is funded by the grant contract SFRH/BD/122365/2016 (Fundação para a Ciência e a Tecnologia). Guilherme Aresta is funded by the grant contract SFRH/BD/120435/2016 (Fundação para a Ciência e a Tecnologia). José Rouco is funded by the grant contract SFRH/BPD/79154/2011 (Fundação para a Ciência e a Tecnologia).
                Categories
                Research Article
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
                Biology and Life Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Anatomy
                Histology
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Biopsy
                Computer and Information Sciences
                Neural Networks
                Biology and Life Sciences
                Neuroscience
                Neural Networks
                Research and Analysis Methods
                Imaging Techniques
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Staining
                Group-Specific Staining
                Hematoxylin Staining
                Custom metadata
                The dataset used for the development of the method and the developed code are publicly available via https://rdm.inesctec.pt/dataset/nis-2017-003.

                Uncategorized
                Uncategorized

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