Multi-modal AI for comprehensive breast cancer prognostication

Treatment selection in breast cancer is guided by molecular subtypes and clinical characteristics. Recurrence risk assessment plays a crucial role in personalizing treatment. Current methods, including genomic assays, have limited accuracy and clinical utility, leading to suboptimal decisions for many patients. We developed a test for breast cancer patient stratification based on digital pathology and clinical characteristics using novel AI methods. Specifically, we utilized a vision transformer-based pan-cancer foundation model trained with self-supervised learning to extract features from digitized H&E-stained slides. These features were integrated with clinical data to form a multi-modal AI test predicting cancer recurrence and death. The test was developed and evaluated using data from a total of 8,161 breast cancer patients across 15 cohorts originating from seven countries. Of these, 3,502 patients from five cohorts were used exclusively for evaluation, while the remaining patients were used for training. Our test accurately predicted our primary endpoint, disease-free interval, in the five external cohorts (C-index: 0.71 [0.68-0.75], HR: 3.63 [3.02-4.37, p<0.01]). In a direct comparison (N=858), the AI test was more accurate than Oncotype DX, the standard-of-care 21-gene assay, with a C-index of 0.67 [0.61-0.74] versus 0.61 [0.49-0.73], respectively. Additionally, the AI test added independent information to Oncotype DX in a multivariate analysis (HR: 3.11 [1.91-5.09, p<0.01)]). The test demonstrated robust accuracy across all major breast cancer subtypes, including TNBC (C-index: 0.71 [0.62-0.81], HR: 3.81 [2.35-6.17, p=0.02]), where no diagnostic tools are currently recommended by clinical guidelines. These results suggest that our AI test can improve accuracy, extend applicability to a wider range of patients, and enhance access to treatment selection tools.

3D-GMIC: an efficient deep neural network to find small objects in large 3D images

3D imaging enables a more accurate diagnosis by providing spatial information about organ anatomy. However, using 3D images to train AI models is computationally challenging because they consist of tens or hundreds of times more pixels than their 2D counterparts. To train with high-resolution 3D images, convolutional neural networks typically resort to downsampling them or projecting them to two dimensions. In this work, we propose an effective alternative, a novel neural network architecture that enables computationally efficient classification of 3D medical images in their full resolution. Compared to off-the-shelf convolutional neural networks, 3D-GMIC uses 77.98%-90.05% less GPU memory and 91.23%-96.02% less computation. While our network is trained only with image-level labels, without segmentation labels, it explains its classification predictions by providing pixel-level saliency maps. On a dataset collected at NYU Langone Health, including 85,526 patients with full-field 2D mammography (FFDM), synthetic 2D mammography, and 3D mammography (DBT), our model, the 3D Globally-Aware Multiple Instance Classifier (3D-GMIC), achieves a breast-wise AUC of 0.831 (95% CI: 0.769-0.887) in classifying breasts with malignant findings using DBT images. As DBT and 2D mammography capture different information, averaging predictions on 2D and 3D mammography together leads to a diverse ensemble with an improved breast-wise AUC of 0.841 (95% CI: 0.768-0.895). Our model generalizes well to an external dataset from Duke University Hospital, achieving an image-wise AUC of 0.848 (95% CI: 0.798-0.896) in classifying DBT images with malignant findings.

Meta-repository of screening mammography classifiers

Artificial intelligence (AI) is transforming medicine and showing promise in improving clinical diagnosis. In breast cancer screening, several recent studies show that AI has the potential to improve radiologists' accuracy, subsequently helping in early cancer diagnosis and reducing unnecessary workup. As the number of proposed models and their complexity grows, it is becoming increasingly difficult to re-implement them in order to reproduce the results and to compare different approaches. To enable reproducibility of research in this application area and to enable comparison between different methods, we release a meta-repository containing deep learning models for classification of screening mammograms. This meta-repository creates a framework that enables the evaluation of machine learning models on any private or public screening mammography data set. At its inception, our meta-repository contains five state-of-the-art models with open-source implementations and cross-platform compatibility. We compare their performance on five international data sets: two private New York University breast cancer screening data sets as well as three public (DDSM, INbreast and Chinese Mammography Database) data sets. Our framework has a flexible design that can be generalized to other medical image analysis tasks. The meta-repository is available at https://www.github.com/nyukat/mammography_metarepository.