Relationship between Aldehyde Dehydrogenase, PD-L1 and Tumor-Infiltrating Lymphocytes with Pathologic Response and Survival in Breast Cancer

SIMPLE SUMMARY: Aldehyde dehydrogenase 1A1 (ALDH1A1) can be used to identify breast cancer stem cells (CSC). Interaction between CSC and the tumor microenvironment might be related to the treatment response, relapse and death. The aim of this retrospective, historical cohort study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs), assessed through immunohistochemistry, in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer tumors, and its association with clinicopathological characteristics and survival. In this study, tumors with positive ALDH1A1 expression also presented positive PD-L1 expression, higher infiltration of lymphocytes and achieved higher response to treatment. It is crucial to understand the possible implication of these biomarkers on neoadjuvant treatment response in certain subtypes of breast cancer as well as its prognostic role in early and locally advanced breast tumors, as they might be possible targets for promising treatments as immunotherapy. ABSTRACT: Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3–87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.