High AURKA Expression Linked to Poorer Outcomes in ER+/HER2− Breast Cancer

Researchers analyzed publicly available bulk-tumor transcriptomic datasets from 8,896 patients with breast cancer, alongside single-cell RNA sequencing data, to examine the biological and clinical significance of Aurora kinase A (AURKA). Analyses focused on ER+/HER2− disease, classifying tumors as AURKA-high or AURKA-low using each cohort’s median expression. Outcomes included tumor characteristics, survival, and response to neoadjuvant chemotherapy.

Higher AURKA expression was associated with histological grade, Ki-67 expression, genomic instability, mutational burden, and DNA repair-related gene expression (all p<0.001). Cell-cycle pathways were enriched across three major datasets. Higher expression was also associated with greater estimated infiltration of several immune-cell populations. AURKA-low tumors showed enrichment of pathways including epithelial–mesenchymal transition and angiogenesis.

Clinically, higher AURKA expression was associated with worse survival and with pathological complete response after neoadjuvant chemotherapy in three of nine ER+/HER2− cohorts. Expression decreased after chemotherapy in all three paired cohorts assessed without subtype stratification. The supplied results do not provide absolute response rates or survival effect sizes.

These findings support further investigation of AURKA as a marker of tumor biology, rather than its immediate use for treatment selection. The observational, secondary analyses cannot establish causality, and the chemotherapy-response association was inconsistent across cohorts. Cohort-specific expression thresholds also do not establish a standardized clinical cutoff.