Abstract
Immune activation plays an important role in achieving the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer. We evaluated how the immune response contributes to various therapeutic effects. This study was conducted on 43 patients with stages II-IV breast cancer who received preoperative chemotherapy followed by surgery. Peripheral natural killer (pNK) cell activity and the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratio (PLR) were assessed before and after chemotherapy. Tumor-infiltrating lymphocytes (TILs) and levels of 14 tumor microenvironmental factors, analyzed by next-generation sequencing, were assessed in formalin-fixed, paraffin-embedded sections of preoperative biopsy samples and surgical specimens. Univariate analysis showed that grade 2 (G2) and better therapeutic effects were significantly associated with human epidermal growth factor receptor 2 (HER-2)-positive cancer, lower PLRs, and higher NK cell and interleukin-6 levels after chemotherapy. The disappearance of axillary lymph-node metastasis was significantly associated with HER-2-positive cancer; increased pNK cell activity and lower PLRs and vascular endothelial growth factor (VEGF) levels after chemotherapy; and increased cytotoxic T lymphocyte antigen 4 (CTLA-4) levels in regulatory T cells (Tregs) and ≥5% TILs before chemotherapy. Multivariate analysis showed that G2 and better therapeutic effects tended to be associated with higher NK cell levels after chemotherapy (odds ratio = 1.02; 95% confidence interval, 0.99-1.05; P = 0.07). The activation of local and systemic immune responses by downregulation of immunosuppressive factors, such as VEGF and CTLA-4 in Tregs, had variable pathological and therapeutic effects after preoperative chemotherapy in patients with breast cancer.