Characteristics of the clinicopathology and immune microenvironment of the basal-like phenotype in HR+/HER2-breast cancer

Abstract Background Expression of basal-like markers (BMs) is usually observed in triple-negative breast cancer (TNBC) and HER2-overexpressing breast cancer and is related to poor prognosis. Recently, some have reported that BM is expressed in 7.8%-27.1% of HR+/HER2- breast cancers (basal-like phenotype, BM+ BCs), but their biological behaviours remain controversial. This study aimed to compare the differences in clinicopathologic features, clinical outcomes and benefit from adjuvant regimens between BM+ BCs and nonbasal-like phenotype breast cancer (BM- BCs) and evaluate their tumour immune microenvironment.Methods BM+ BCs were defined as EGFR- and/or CK5/6-positive (n=150). Overall, 180 BM- BCs were selected as the control cohort. Clinicopathological characteristics were retrospectively collected. Univariate and multivariate analyses were used to assess the relationship between disease-free survival (DFS), overall survival (OS) and BM status. Stromal tumour-infiltrating lymphocytes (sTILs) were evaluated on haematoxylin & eosin-stained slides, and CD3, CD8, FOPX3, chemokine (C-X-C motif) ligand 13 (CXCL13), CD68, PD-1 and PD-L1 were stained by IHC.Results Compared to BM- BCs, BM+ BCs were more frequently diagnosed at a younger age and had a higher tumour stage, histological grade and necrosis. No obvious differences were seen in lymphovascular invasion or lymph node metastasis. Lower ER and PR expression and higher Ki-67 expression were observed in BM+ BCs. Overall, 62.8% BM+ BCs had p53 mutations. Shorter DFS and OS were related to BM+ BCs (p=0.021 and 0.018, respectively). In multivariate analysis, CK5/6 and clinical stage were independent prognostic factors for DFS and OS. BM+ BCs had a higher proportion of high sTILs with increased CD3, CD8, FOXP3, CXCL13 and CD68 expression. PD-1 and PD-L1 expression was positively related to BM+ BCs.Conclusion Our study demonstrated that more aggressive morphologic features and worse prognosis were associated with BM+ BCs, and its immune-activated status may support new therapeutic strategies, such as immunotherapy, as a potential treatment.