High expression of the five-gene signature was associated with increased infiltration of cytotoxic and antigen-presenting immune cells, consistent with an immune-activated tumor microenvironment, and was confirmed by qRT-PCR analysis.<h4>Conclusion</h4>This study establishes a rigorously validated ANN-based immune gene signature for predicting response to neoadjuvant chemotherapy in HER2-negative breast cancer, providing a potential tool for pretreatment risk stratifictableation and individualized therapeutic decision-making. Here, ERBB2 is linked to breast cancer.