Abstract ES11-1: The biology and plasticity of residual disease after neoadjuvant treatment

Abstract

Abstract Breast cancer neoadjuvant treatment is becoming more prevalent, and has emerged as a valuable tool to downstage tumors, to identify predictors of responsiveness, and to potentially adapt therapeutic interventions to that individual’s residual disease if present. This has led to increasingly complex patient management and the development of many clinical trials specifically designed for those with residual disease. However, the basic biology of residual disease, how it relates to pre-treated disease, and how it could be used for prognostic and redictive benefits, are still relatively unknown. In this session I will cover a number of studies that have specifically studied breast tumors before and after neoadjuvant treatment, with a focus on changes within the tumor cell population, including acquisition of epithelial-to-mesenchymal (EMT) and stem-like properties. In addition, alterations to immune cell dynamics in the tumor microenvironment, the plasticity of post-treatment phenotypes, and how these features impact the treatment paradigm based upon residual disease, will also be discussed. Multiple factors likely contribute to the poor prognosis associated with residual disease. Human breast tumors that remain following either chemotherapy, or endocrine therapy, often show an enrichment of gene expression signatures associated with tumor-initiating cells and EMT, suggesting that intrinsic tumor characteristics may contribute to selection of resistant populations. Additionally, residual tumors may show a variety of genomic aberrations at higher frequency than found in primary tumors, suggesting that resistance pathways may be selected for during neoadjuvant treatment. Tumor extrinsic factors, particularly the interaction between tumor and immune cells, are also altered by breast cancer neoadjuvant therapies. Nevertheless, there is hope that these residual disease specific alterations may provide key susceptibilities to other treatments. Lastly, defining predictive biomarkers from residual disease has been difficult. In addition to the variety and complexity of resistance mechanisms that lead to residual disease, questions regarding tumor plasticity and the duration of post-treatment changes complicate the analysis of residual breast cancers specimens. An improved understanding of the biology of residual breast cancers will be critical as we develop novel treatment strategies for those with residual disease. Citation Format: C Perou. The biology and plasticity of residual disease after neoadjuvant treatment [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES11-1.