Predictive and prognostic biomarker testing in invasive breast cancer

Surgical pathologists play an important role in ordering and interpreting biomarker testing for prognostic and predictive purposes. In invasive breast cancer, these biomarkers include hormone receptors, HER2 expression, multi-gene expression assays, checkpoint inhibitor staining, single gene mutation status, and genomic findings. Additionally, there are tests that predict response to “tumor-agnostic” drugs targeting gene-specific alterations or protein expression changes, regardless of tumor type. The assays employed to assess these biomarkers range from immunohistochemistry to RNA expression to next-generation sequencing. Each assay has specific indications and technical pitfalls. The pathologist must select the correct specimen, choose the area for microdissection, and consider cellularity and tissue adequacy. Often, the pathologist will also provide interpretation of the results. This review will provide an overview of these biomarker tests in breast cancer, describe their indications and utilization, and list some of their challenges. It will serve as a practical reference for pathologists in their integral role in patient care.