Biological insights and novel biomarker discovery through deep learning approaches in breast cancer histopathology

Breast cancer remains a highly prevalent disease with considerable inter- and intra-tumoral heterogeneity complicating prognostication and treatment decisions. The utilization and depth of genomic, transcriptomic and proteomic data for cancer has exploded over recent times and the addition of spatial context to this information, by understanding the correlating morphologic and spatial patterns of cells in tissue samples, has created an exciting frontier of research, histo-genomics. At the same time, deep learning (DL), a class of machine learning algorithms employing artificial neural networks, has rapidly progressed in the last decade with a confluence of technical developments - including the advent of modern graphic processing units (GPU), allowing efficient implementation of increasingly complex architectures at scale; advances in the theoretical and practical design of network architectures; and access to larger datasets for training - all leading to sweeping advances in image classification and object detection. In this review, we examine recent developments in the application of DL in breast cancer histology with particular emphasis of those producing biologic insights or novel biomarkers, spanning the extraction of genomic information to the use of stroma to predict cancer recurrence, with the aim of suggesting avenues for further advancing this exciting field.