A comprehensive review on the pathologic evaluation of breast cancer after neoadjuvant systemic therapy

Neoadjuvant systemic therapy (NST) is increasingly used across biologic subtypes of breast cancer and includes cytotoxic chemotherapy, HER2-directed therapy, immunotherapy, endocrine therapy, and selected investigational approaches. The expanding therapeutic landscape creates new challenges for pathologists, including recognition of therapy-related morphologic alterations, localization and sampling of the tumor bed, measurement of discontinuous residual invasive carcinoma, assessment of treated lymph nodes, calculation of residual cancer burden (RCB), post-treatment ypTNM staging, and interpretation of biomarkers in residual disease. This review summarizes therapy-associated pathologic changes and provides a practical approach to specimen evaluation and reporting. Emphasis is placed on comparing ypTNM and RCB measurements, diagnostic pitfalls, and circumstances in which repeating biomarker assessment may be clinically informative. Emerging strategies such as image-guided biopsy to identify exceptional responders and preoperative radiotherapy are discussed as newer approaches.