Grading of invasive breast carcinoma: the way forward

Histologic grading has been a simple and inexpensive method to assess tumor behavior and prognosis of invasive breast cancer grading, thereby identifying patients at risk for adverse outcomes, who may be eligible for (neo)adjuvant therapies. Histologic grading needs to be performed accurately, on properly fixed specimens, and by adequately trained dedicated pathologists that take the time to diligently follow the protocol methodology. In this paper, we review the history of histologic grading, describe the basics of grading, review prognostic value and reproducibility issues, compare performance of grading to gene expression profiles, and discuss how to move forward to improve reproducibility of grading by training, feedback and artificial intelligence algorithms, and special stains to better recognize mitoses. We conclude that histologic grading, when adequately carried out, remains to be of important prognostic value in breast cancer patients.