Prognostic and predictive parameters in breast pathology: a pathologist's primer

The pathologist's role in the breast cancer treatment team has evolved from rendering a diagnosis of breast cancer, to providing a growing list of prognostic and predictive parameters such that individualized treatment decisions can be made based on likelihood of benefit from additional treatments and potential benefit from specific therapies. In all stages, ER and HER2 status help segregate breast cancers into treatment groups with similar outcomes and treatment response rates, however, traditional pathologic parameters such as favorable histologic subtype, size, lymph node status, and Nottingham grade also have remained clinically relevant in early stage disease decision-making. This is especially true for the most common subtype of breast cancer; ER positive, HER2 negative disease. For this same group of breast cancers, an ever-expanding list of gene-expression panels also can provide prediction and prognostication about potential chemotherapy benefit beyond standard endocrine therapies, with the 21-gene Recurrence Score, currently the only prospectively validated predictive test for this purpose. In the more aggressive ER-negative cancer subtypes, response to neoadjuvant therapy and` the extent of tumor infiltrating lymphocytes (TILs) are more recently recognized powerful prognostic parameters, and clinical guidelines now offer additional treatment options for those high-risk patients with residual cancer after standard neoadjuvant therapy. In stage four disease, predictive tests like germline BRCA status, tumor PIK3CA mutation status (in ER+ metastatic disease) and PDL-1 status (in triple negative metastatic disease) are now used to determine additional new treatment options. The objective of this review is to describe the latest in prognostic and predictive parameters in breast cancer as they are relevant to standard pathology reporting and how they are used in breast cancer clinical treatment decisions.