Automatic methods for early detection of breast cancer on mammography can significantly decrease mortality. Broad uptake of those methods in hospitals is currently hindered because the methods have too many constraints. They assume annotations available for single images or even regions-of-interest (ROIs), and a fixed number of images per patient. Both assumptions do not hold in a general hospital setting. Relaxing those assumptions results in a weakly supervised learning setting, where labels are available per case, but not for individual images or ROIs. Not all images taken for a patient contain malignant regions and the malignant ROIs cover only a tiny part of an image, whereas most image regions represent benign tissue. In this work, we investigate a two-level multi-instance learning (MIL) approach for case-level breast cancer prediction on two public datasets (1.6k and 5k cases) and an in-house dataset of 21k cases. Observing that breast cancer is usually only present in one side, while images of both breasts are taken as a precaution, we propose a domain-specific MIL pooling variant. We show that two-level MIL can be applied in realistic clinical settings where only case labels, and a variable number of images per patient are available. Data in realistic settings scales with continuous patient intake, while manual annotation efforts do not. Hence, research should focus in particular on unsupervised ROI extraction, in order to improve breast cancer prediction for all patients.
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