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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.

Background: Cytoplasmatic expression of Aldehyde dehydrogenase 1 A1 (ALDH1A1) has been identified as a cancer stem cell marker and related to an unfavorable prognosis. However, nuclear expression of ALDH1A1 has not been described in breast cancer (BC) patients yet. Methods: A retrospective, historical cohort study of patients diagnosed with early or locally advanced triple negative (TN) and human epidermal growth factor receptor 2 positive (HER2+) BC treated with neoadjuvant chemotherapy was conducted. Patients who had an available tumor sample from the diagnosis and who underwent surgery after the neoadjuvant treatment were included. Metastatic patients and non-evaluative biopsy sample cases were excluded. Immunostaining against ALDH1A1 was performed. The aim of this study was to assess the expression of nuclear ALDH1A1 in BC and its relation with clinicopathological features and outcomes.Results: 75 patients were analyzed (100% women, mean age 53.6±11.7 years, 42.7% TN, 57.3% HER2+ tumors). 28% had obesity, 32 (42.7%) had a tumor size ≤5 cm and 52 (69.3%) positive lymph nodes. 40 (53.3%) patients had cytoplasmatic ALDH1A1 expression. From them, 18 (24%) also expressed nuclear ALDH1A1 staining and 22 (29.3%) only had cytoplasmatic expression. 57 (76%) patients had negative nuclear ALDH1A1. 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%) died. Patients with nuclear ALDH1A1 had higher prevalence of obesity when comparing to exclusively positive cytoplasmatic ALDH1A1 (p = 0.003) and versus those with negative ALDH1A1 expression (p = 0.017); and also, smaller size compared to those without nuclear ALDH1A1 staining (p = 0.044). Furthermore, in patients with positive nuclear ALDH1A1 a tendency to superior disease-free survival (DFS) and overall survival (OS) was observed when compared to positive cytoplasmatic and negative ALDH1A1 tumors, albeit not statistically significant. Conclusions: In this cohort, nuclear positive expression of ALDH1A1 was higher in patients with obesity and smaller tumors. Patients with positive nuclear ALDH1A1 carcinomas appear to have better DFS and OS, although this was not statistically significant. Further research studies are needed to understand the functions of this enzyme and its possible role as a predictive and prognostic marker in BC.

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