Abstract

Breast cancer, the most common malignant tumor among women worldwide, remains an incurable disease once it has spread to distant organs. The human epidermal growth factor receptor 2-positive and triple-negative molecular subtypes are associated with an increased risk of developing breast cancer. This study aimed to investigate the potential impact of crucial neutrophil extracellular traps-related genes on the survival of patients with human epidermal growth factor receptor 2-positive breast cancer and triple-negative breast cancer. 69 neutrophil extracellular traps-related genes were selected as the study subjects to their association with survival, immune infiltration impacts, interaction networks, and potential drugs for human epidermal growth factor receptor 2-positive breast cancer/triple-negative breast cancer. Using least absolute shrinkage and selection operator regression models based on 69 candidate neutrophil extracellular traps-related genes for predicting overall survival and progressionfree survival, we identified 16 key human epidermal growth factor receptor 2 neutrophil extracellular trap genes and 4 key triple-negative breast cancer genes. We identified four core neutrophil extracellular traps-related genes: Alkaline phosphatase, biomineralization associated, autophagy related 7, colony stimulating factor 3 receptor, and cathelicidin antimicrobial peptide responsive element binding protein 5, which may influence breast cancer progression through mechanisms associated with neutrophil extracellular traps. The key neutrophil extracellular traps-related genes were closely correlated with neutrophils, myeloid dendritic cells macrophage, clusters of differentiation 4⁺ and clusters of differentiation 8⁺ T cells. Moreover, potential sensitizing drugs for human epidermal growth factor receptor 2-positive breast cancer and triple-negative breast cancer treatment identified using the genomics of therapeutics response portal and genomics of drug sensitivity in cancer databases may include; SB52334, 17-alkyladenine DNA glycosylase, bromodomain containing-K51490254, CAY10618, GMX-1778, daporinad, serdemetan, CIL70 and panobinostat. In summary, the key neutrophil extracellular traps-related genes may play important roles in the growth and development of human epidermal growth factor receptor 2-positive breast cancer and triple-negative breast cancer. They can impact different immune cells, tumor immune microenvironment and predict overall survival and progression-free survival of breast cancer.