Association of multiple immune markers with survival outcomes, treatment response, and axillary lymph node status in HER2 + breast cancer patients undergoing neoadjuvant chemotherapy

Abstract Objective To evaluate the expression levels of tumor-infiltrating lymphocytes (TILs) and their subtypes in HER2-positive breast cancer (HER2 + BC) patients undergoing neoadjuvant chemotherapy (NAC) and to investigate their association with survival outcomes, pathological complete response (pCR), and axillary lymph node (aLNs) status. Methods Thirty-one patients who experienced recurrence or metastasis were selected as the case group from 490 patients who were diagnosed with HER2 + BC and underwent NAC in conjunction with surgery. An additional 31 patients with comparable clinicopathological characteristics but no recurrence or metastasis were selected as the control group. Immunohistochemical analysis of pathology sections was performed to examine the expression of TILs, CD3, CD4, CD8, CD20, FoxP3 and PD-L1. Results Patients with high CD3 expression group and those with high cytoplasmic PD-L1 (cPD-L1) expression group showed significantly better progression-free survival (PFS) ( P = 0.043, P = 0.049, respectively). Multivariate Cox analysis revealed that CD3 ( P = 0.033, HR = 0.806) and cPD-L1 ( P = 0.025, HR = 0.748) were independent predictors of PFS. The expression levels of CD4 in pCR group was significant higher than non-pCR group ( P = 0.047). There was no significant difference in immune markers between the aLNs metastasis and non-metastasis groups. Conclusions For HER2 + BC treated with NAC, high expression of CD3 and cPD-L1 is associated with improved PFS. Furthermore, CD3 and cPD-L1 have been identified as independent prognostic factors. Additionally, high CD4 expression predicts improved pCR.