High Expression of Aurora Kinase A (AURKA) is Associated with Aggressive Tumor Biology and Therapeutic Response in ER+/HER2− Breast Cancer

Abstract Background Aurora kinase A ( AURKA ) is a serine/threonine kinase that regulates mitotic entry, spindle assembly, and chromosomal segregation. AURKA overexpression has been linked to multiple malignancies. The biological and clinical significance of AURKA expression within estrogen receptor-positive, human epidermal growth factor receptor 2-negative (ER+/HER2−) breast cancer has yet to be fully elucidated. Methods A total of 8896 patients were analyzed across bulk transcriptomic datasets. Single-cell RNA sequencing datasets were also analyzed. ER+/HER2− tumors were divided into AURKA -high or -low groups according to the median AURKA expression within each cohort. Results AURKA expression was associated with Nottingham histological grade and Ki-67 expression ( p < 0.001) and enrichment of cell cycle-related pathways across The Cancer Genome Atlas, Molecular Taxonomy of Breast Cancer International Consortium, and Sweden Cancerome Analysis Network-Breast datasets (all false discovery rate <0.01; normalized enrichment score >2). AURKA expression was associated with genomic instability, increased mutational burden and enhanced DNA repair-related genes (all p < 0.001) and with increased infiltration of type 1 and 2 T-helper cells, M1-like macrophages, and total macrophages (all p < 0.001). Conversely, AURKA -low tumors were enriched for epithelial mesenchymal transition, myogenesis, coagulation, angiogenesis, and transforming growth factor-β signaling pathways (most false discovery rate <0.01) and higher cancer stem cells score (all p < 0.001). Clinically, higher AURKA expression was associated with pathological complete response after neoadjuvant chemotherapy in three of nine ER+/HER2− cohorts and with worse survival outcomes. AURKA expression also decreased after neoadjuvant chemotherapy in all three paired cohorts analyzed, regardless of subtype. Conclusion High AURKA expression was associated with a highly proliferative, immune-engaged tumor phenotype and with worse survival despite better therapeutic response in ER+/HER2− breast cancer.