Breast cancer comprises a heterogeneous group of tumor subtypes, whether defined by immunohistochemistry of key proteins, RNA expression profiles, or genetic alterations, and each of these subtypes may benefit from a distinct treatment approach. However, there can be striking heterogeneity within tumors, which may pose challenges to the development of personalized approaches to therapy. Intratumor heterogeneity can be divided into three main categories: genetic, phenotypic, and microenvironmental. Here, we review technologies to interrogate these three categories of heterogeneity in patient samples, as well as the current state of understanding of these categories in breast cancer, from cell to cell, across different regions of the same tumor mass, across treatment, and across metastasis. Efforts to characterize tumor heterogeneity longitudinally will be crucial to the development of personalized oncology for breast cancer.

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