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      Machine Learning techniques in breast cancer prognosis prediction: A primary evaluation

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          Abstract

          More than 750 000 women in Italy are surviving a diagnosis of breast cancer. A large body of literature tells us which characteristics impact the most on their prognosis. However, the prediction of each disease course and then the establishment of a therapeutic plan and follow‐up tailored to the patient is still very complicated. In order to address this issue, a multidisciplinary approach has become widely accepted, while the Multigene Signature Panels and the Nottingham Prognostic Index are still discussed options. The current technological resources permit to gather many data for each patient. Machine Learning (ML) allows us to draw on these data, to discover their mutual relations and to esteem the prognosis for the new instances. This study provides a primary evaluation of the application of ML to predict breast cancer prognosis. We analyzed 1021 patients who underwent surgery for breast cancer in our Institute and we included 610 of them. Three outcomes were chosen: cancer recurrence (both loco‐regional and systemic) and death from the disease within 32 months. We developed two types of ML models for every outcome (Artificial Neural Network and Support Vector Machine). Each ML algorithm was tested in accuracy (=95.29%‐96.86%), sensitivity (=0.35‐0.64), specificity (=0.97‐0.99), and AUC (=0.804‐0.916). These models might become an additional resource to evaluate the prognosis of breast cancer patients in our daily clinical practice. Before that, we should increase their sensitivity, according to literature, by considering a wider population sample with a longer period of follow‐up. However, specificity, accuracy, minimal additional costs, and reproducibility are already encouraging.

          Abstract

          Machine Learning (ML) allows us to discover relations between prognostic factors and to predict breast cancer prognosis. These models might become an additional resource in our daily clinical practice.

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          Most cited references35

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          20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.

          The administration of endocrine therapy for 5 years substantially reduces recurrence rates during and after treatment in women with early-stage, estrogen-receptor (ER)-positive breast cancer. Extending such therapy beyond 5 years offers further protection but has additional side effects. Obtaining data on the absolute risk of subsequent distant recurrence if therapy stops at 5 years could help determine whether to extend treatment.
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            Machine Learning for Medical Imaging.

            Machine learning is a technique for recognizing patterns that can be applied to medical images. Although it is a powerful tool that can help in rendering medical diagnoses, it can be misapplied. Machine learning typically begins with the machine learning algorithm system computing the image features that are believed to be of importance in making the prediction or diagnosis of interest. The machine learning algorithm system then identifies the best combination of these image features for classifying the image or computing some metric for the given image region. There are several methods that can be used, each with different strengths and weaknesses. There are open-source versions of most of these machine learning methods that make them easy to try and apply to images. Several metrics for measuring the performance of an algorithm exist; however, one must be aware of the possible associated pitfalls that can result in misleading metrics. More recently, deep learning has started to be used; this method has the benefit that it does not require image feature identification and calculation as a first step; rather, features are identified as part of the learning process. Machine learning has been used in medical imaging and will have a greater influence in the future. Those working in medical imaging must be aware of how machine learning works. ©RSNA, 2017.
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              Prognostic significance of progesterone receptor-positive tumor cells within immunohistochemically defined luminal A breast cancer.

              Current immunohistochemical (IHC)-based definitions of luminal A and B breast cancers are imperfect when compared with multigene expression-based assays. In this study, we sought to improve the IHC subtyping by examining the pathologic and gene expression characteristics of genomically defined luminal A and B subtypes. Gene expression and pathologic features were collected from primary tumors across five independent cohorts: British Columbia Cancer Agency (BCCA) tamoxifen-treated only, Grupo Español de Investigación en Cáncer de Mama 9906 trial, BCCA no systemic treatment cohort, PAM50 microarray training data set, and a combined publicly available microarray data set. Optimal cutoffs of percentage of progesterone receptor (PR) -positive tumor cells to predict survival were derived and independently tested. Multivariable Cox models were used to test the prognostic significance. Clinicopathologic comparisons among luminal A and B subtypes consistently identified higher rates of PR positivity, human epidermal growth factor receptor 2 (HER2) negativity, and histologic grade 1 in luminal A tumors. Quantitative PR gene and protein expression were also found to be significantly higher in luminal A tumors. An empiric cutoff of more than 20% of PR-positive tumor cells was statistically chosen and proved significant for predicting survival differences within IHC-defined luminal A tumors independently of endocrine therapy administration. Finally, no additional prognostic value within hormonal receptor (HR) -positive/HER2-negative disease was observed with the use of the IHC4 score when intrinsic IHC-based subtypes were used that included the more than 20% PR-positive tumor cells and vice versa. Semiquantitative IHC expression of PR adds prognostic value within the current IHC-based luminal A definition by improving the identification of good outcome breast cancers. The new proposed IHC-based definition of luminal A tumors is HR positive/HER2 negative/Ki-67 less than 14%, and PR more than 20%.

                Author and article information

                Contributors
                corrado.doc@gmail.com
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                10 March 2020
                May 2020
                : 9
                : 9 ( doiID: 10.1002/cam4.v9.9 )
                : 3234-3243
                Affiliations
                [ 1 ] SSD Breast Unit – ASST‐Settelaghi Varese Senology Research Center Department of Medicine University of Insubria Varese Italy
                Author notes
                [*] [* ] Correspondence

                Corrado Chiappa, Senology Research Center, Department of Medicine, University of Insubria – Varese, SSD Breast Unit, ASST‐Settelaghi di Varese, Ospedale di Circolo Fondazione Macchi, Via Guicciardini, 9, 21100 Varese, Italy.

                Email: corrado.doc@ 123456gmail.com

                Author information
                https://orcid.org/0000-0002-6153-3156
                Article
                CAM42811
                10.1002/cam4.2811
                7196042
                32154669
                7d891c12-db9b-40fa-a932-4759f82f805c
                © 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 05 July 2019
                : 28 November 2019
                : 13 December 2019
                Page count
                Figures: 5, Tables: 5, Pages: 10, Words: 5200
                Categories
                Original Research
                Cancer Prevention
                Original Research
                Custom metadata
                2.0
                May 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.1 mode:remove_FC converted:02.05.2020

                Oncology & Radiotherapy
                algorithm,artificial neural network (ann),breast cancer,predictive models,support vector machine (svm)

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