Issues and missed opportunities in lymph node assessment after neoadjuvant chemotherapy

Abstract

Assessment of axillary lymph nodes in breast cancer patients following neoadjuvant chemotherapy (NACT) is a crucial part of the clinical and pathological assessment of the disease and has prognostic and management implications. This, however, currently lacks standardisation and focuses only on the number of lymph nodes with metastases still present, the largest metastasis, and the presence of pathological complete response. Potential changes in any residual disease or within the lymph node parenchyma are not examined. Novel methods of more nuanced approaches are rare in the literature, even when considering multiple cancer types, but can offer an insight into the potential additional information to be gained and improvement in patient stratification. Given how common NACT is as the backbone of cancer therapy, there is a surprising lack of research into the lymph node response and determination of the biological factors driving what is seen histologically. Furthermore, with NACT now being administered alongside immunotherapy, there is an increasing need to understand the functional and architectural changes induced in the lymph nodes by metastatic tumour and systemic therapies. This review summarises current approaches, with breast cancer as an exemplar, and discusses the literature investigating a possible more granular approach to lymph node assessment after NACT. Translating these multiple carcinoma studies to breast cancer patients may prompt tissue-based research and, with clinical validation studies, changes to the reporting of lymph node response, for example percentage of viable tumour and immunological architectural features such as germinal centres. © 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.