Understanding Breast Cancers through Spatial and High-Resolution Visualization Using Imaging Technologies

SIMPLE SUMMARY: Breast cancer tissue is not composed solely of cancer cells but exists in a complex microenvironment consisting of surrounding cells and proteins, including fibroblasts, immune cells, blood vessels, and extracellular matrix. The malignant transformation and metastasis of breast cancer occur due to the interaction between cancer cells and surrounding environmental cells and/or proteins. Therefore, it is extremely important to visualize the three-dimensional structure of breast cancer cells and their surrounding environment both invasively and noninvasively and to understand their relationship; this review aims to provide an overview of the tissue transparency techniques, optical observation methods, spatial transcriptomic analysis, and noninvasive medical imaging methods used for understanding malignant breast cancers. ABSTRACT: Breast cancer is the most common cancer affecting women worldwide. Although many analyses and treatments have traditionally targeted the breast cancer cells themselves, recent studies have focused on investigating entire cancer tissues, including breast cancer cells. To understand the structure of breast cancer tissues, including breast cancer cells, it is necessary to investigate the three-dimensional location of the cells and/or proteins comprising the tissues and to clarify the relationship between the three-dimensional structure and malignant transformation or metastasis of breast cancers. In this review, we aim to summarize the methods for analyzing the three-dimensional structure of breast cancer tissue, paying particular attention to the recent technological advances in the combination of the tissue-clearing method and optical three-dimensional imaging. We also aimed to identify the latest methods for exploring the relationship between the three-dimensional cell arrangement in breast cancer tissues and the gene expression of each cell. Finally, we aimed to describe the three-dimensional imaging features of breast cancer tissues using noninvasive photoacoustic imaging methods.