Abstract 7607: Single-cell genomics study before and after neoadjuvant therapy for triple-negative breast cancer

Abstract Breast cancer has become the most common malignant tumor globally. Neoadjuvant chemotherapy (NAC) has become an important treatment option for locally advanced breast cancer, capable of eliminating circulating tumor cells (micrometastases) and achieving downstaging objectives. However, even after completing neoadjuvant chemotherapy or receiving local treatment, some patients may still have residual lesions, which are a key factor in distant recurrence and metastasis. The existing clinical biomarker tests such as CEA, CA-153, and imaging methods are unable to accurately assess the condition early on. Although tissue pathology biopsy of tumor specimens is the gold standard for clinical pathological diagnosis, it also has certain limitations. Traditional high-throughput sequencing technology for breast cancer primarily identifies "driver genes" associated with the occurrence and development of breast cancer. However, it has limitations in identifying genomic structural changes and subclones of breast cancer, and it overlooks the heterogeneity among tumor cells. The emergence of single-cell RNA sequencing (scRNA-seq) technology can detect these heterogeneous individuals, decode the heterogeneity of breast cancer cells, refine molecular subtypes, and open up new pathways to overcome drug resistance. We collected samples from 6 patients with locally advanced triple-negative breast cancer (ER-, PR-, HER2-negative, defined as HER2 immunohistochemistry 0, 1+ or 2+ but FISH-negative). We compared the cell subgroups and their gene expression in biopsy specimens before neoadjuvant chemotherapy with those in post-treatment specimens obtained during surgery, analyzing changes in cell composition in the tumor microenvironment before and after immunotherapy to identify specific cell types potentially contributing to the outcome of immunotherapy, particularly cell subtypes associated with T-cell clonal proliferation. We found that in the group with good neoadjuvant treatment response (Miller-Payne grade 4-5), B cells, CD4+ T cells, CD8+ T cells, and Tregs cells were all significantly downregulated, while endothelial cells and aSMA-positive fibroblast cells were significantly upregulated. By comparing changes in the immune microenvironment between patients with and without T-cell clonal proliferation before and after treatment, we revealed the differentiation patterns of various immune cells in immunotherapy and potential mechanisms of action. Citation Format: Yingkuan Shao, Kailun Xu. Single-cell genomics study before and after neoadjuvant therapy for triple-negative breast cancer abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (6Suppl): Abstract nr 7607.