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      Prediction of HER2-positive breast cancer recurrence and metastasis risk from histopathological images and clinical information via multimodal deep learning

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          Abstract

          HER2-positive breast cancer is a highly heterogeneous tumor, and about 30% of patients still suffer from recurrence and metastasis after trastuzumab targeted therapy. Predicting individual prognosis is of great significance for the further development of precise therapy. With the continuous development of computer technology, more and more attention has been paid to computer-aided diagnosis and prognosis prediction based on Hematoxylin and Eosin (H&E) pathological images, which are available for all breast cancer patients undergone surgical treatment. In this study, we first enrolled 127 HER2-positive breast cancer patients with known recurrence and metastasis status from Cancer Hospital of the Chinese Academy of Medical Sciences. We then proposed a novel multimodal deep learning method integrating whole slide H&E images (WSIs) and clinical information to accurately assess the risk of relapse and metastasis in patients with HER2-positive breast cancer. Specifically, we obtained the whole H&E staining images from the surgical specimens of breast cancer patients, and these images were adjusted to size 512 × 512 pixels. The deep convolutional neural network (CNN) was applied to these images to retrieve image features, which were combined with the clinical data. Based on the combined features. After that, a novel multimodal model was constructed for predicting the prognosis of each patient. The model achieved an area under curve (AUC) of 0.76 in the two-fold cross-validation (CV). To further evaluate the performance of our model, we downloaded the data of all 123 HER2-positive breast cancer patients with available H&E image and known recurrence and metastasis status in The Cancer Genome Atlas (TCGA), which was severed as an independent testing data. Despite the huge differences in race and experimental strategies, our model achieved an AUC of 0.72 in the TCGA samples. As a conclusion, H&E images, in conjunction with clinical information and advanced deep learning models, could be used to evaluate the risk of relapse and metastasis in patients with HER2-positive breast cancer.

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          Most cited references43

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          This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.
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            Deep learning allows computational models that are composed of multiple processing layers to learn representations of data with multiple levels of abstraction. These methods have dramatically improved the state-of-the-art in speech recognition, visual object recognition, object detection and many other domains such as drug discovery and genomics. Deep learning discovers intricate structure in large data sets by using the backpropagation algorithm to indicate how a machine should change its internal parameters that are used to compute the representation in each layer from the representation in the previous layer. Deep convolutional nets have brought about breakthroughs in processing images, video, speech and audio, whereas recurrent nets have shone light on sequential data such as text and speech.
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                Author and article information

                Contributors
                Journal
                Comput Struct Biotechnol J
                Comput Struct Biotechnol J
                Computational and Structural Biotechnology Journal
                Research Network of Computational and Structural Biotechnology
                2001-0370
                23 December 2021
                2022
                23 December 2021
                : 20
                : 333-342
                Affiliations
                [a ]Chifeng Municipal Hospital, Chifeng, Inner Mongolia 024000, China
                [b ]Genies (Beijing) Co., Ltd., Beijing 100102, China
                [c ]Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
                [d ]Department of Pathology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
                [e ]Department of Pathology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
                [f ]Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
                Author notes
                [1]

                These authors contributed equally to this study.

                Article
                S2001-0370(21)00537-7
                10.1016/j.csbj.2021.12.028
                8733169
                35035786
                f35fb481-0bf6-4d43-b840-ee0611ee06c2
                © 2021 Published by Elsevier B.V. on behalf of Research Network of Computational and Structural Biotechnology.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 22 September 2021
                : 12 December 2021
                : 18 December 2021
                Categories
                Research Article

                breast cancer,recurrence,her2,h&e-stained histological images,convolutional neural network

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