Abstract

Following recent US Food and Drug Administration approval, adoption of whole slide imaging in clinical settings may be imminent, and diagnostic accuracy, particularly among challenging breast biopsy specimens, may benefit from computerized diagnostic support tools. To develop and evaluate computer vision methods to assist pathologists in diagnosing the full spectrum of breast biopsy samples, from benign to invasive cancer. In this diagnostic study, 240 breast biopsies from Breast Cancer Surveillance Consortium registries that varied by breast density, diagnosis, patient age, and biopsy type were selected, reviewed, and categorized by 3 expert pathologists as benign, atypia, ductal carcinoma in situ (DCIS), and invasive cancer. The atypia and DCIS cases were oversampled to increase statistical power. High-resolution digital slide images were obtained, and 2 automated image features (tissue distribution feature and structure feature) were developed and evaluated according to the consensus diagnosis of the expert panel. The performance of the automated image analysis methods was compared with independent interpretations from 87 practicing US pathologists. Data analysis was performed between February 2017 and February 2019. Diagnostic accuracy defined by consensus reference standard of 3 experienced breast pathologists. The accuracy of machine learning tissue distribution features, structure features, and pathologists for classification of invasive cancer vs noninvasive cancer was 0.94, 0.91, and 0.98, respectively; the accuracy of classification of atypia and DCIS vs benign tissue was 0.70, 0.70, and 0.81, respectively; and the accuracy of classification of DCIS vs atypia was 0.83, 0.85, and 0.80, respectively. The sensitivity of both machine learning features was lower than that of the pathologists for the invasive vs noninvasive classification (tissue distribution feature, 0.70; structure feature, 0.49; pathologists, 0.84) but higher for the classification of atypia and DCIS vs benign cases (tissue distribution feature, 0.79; structure feature, 0.85; pathologists, 0.72) and the classification of DCIS vs atypia (tissue distribution feature, 0.88; structure feature, 0.89; pathologists, 0.70). For the DCIS vs atypia classification, the specificity of the machine learning feature classification was similar to that of the pathologists (tissue distribution feature, 0.78; structure feature, 0.80; pathologists, 0.82). The computer-based automated approach to interpreting breast pathology showed promise, especially as a diagnostic aid in differentiating DCIS from atypical hyperplasia.

Highlights

  • In 2019, more than 1 million individuals in the United States will undergo a breast biopsy, with an estimated 268 600 patients diagnosed with breast cancer and 3-fold that number receiving a noncancer diagnosis.[1]

  • Whole-slide imaging (WSI), a technology that captures the contents of a glass slide in a multiresolution image, is revolutionizing diagnostic medicine by providing researchers with tools to study diagnostic missteps and develop diagnostic support systems

  • The US health care system will undergo a major shift toward digital pathology, and the resulting need for automated diagnosis tools that can lead to computer-aided diagnostic support systems will be significant

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Summary

Introduction

In 2019, more than 1 million individuals in the United States will undergo a breast biopsy, with an estimated 268 600 patients diagnosed with breast cancer and 3-fold that number receiving a noncancer diagnosis.[1]. An exact estimate of overdiagnosed cases is unknown, several studies[2,3] have hypothesized and estimated its prevalence in breast cancer diagnosis. Whole-slide imaging (WSI), a technology that captures the contents of a glass slide in a multiresolution image, is revolutionizing diagnostic medicine by providing researchers with tools to study diagnostic missteps and develop diagnostic support systems. US Food and Drug Administration regulations limited the use of WSIs to nonclinical purposes, such as research and biorepositories, until April 2017, when the first Food and Drug Administration–approved WSI system for diagnostic medicine was announced.[4] With this development, the US health care system will undergo a major shift toward digital pathology, and the resulting need for automated diagnosis tools that can lead to computer-aided diagnostic support systems will be significant.

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