To explore the heterogeneity of tumor-associated macrophage （TAM） in breast cancer and the functional differences among different TAM subgroups， and analyze the impact of TAM-related genes on the prognosis of triple negative breast cancer （TNBC） patients.

Thirty breast cancer tissue samples and 13 normal breast tissue samples from the GSE161529 dataset were collected. TAM subgroups were identified using the Seurat pipeline and consensus non-negative matrix factorization algorithm. The immune functions of different TAM subgroups were analyzed through GO and immune response enrichment analysis. The tissue samples of 5 TNBC patients from the GSE148673 dataset were collected. Univariate Cox regression and Pearson correlation analysis were used to screen for significant gene pairs related to TAM， and a co-expression network of TAM prognostic genes was constructed. K-means unsupervised clustering was used to get molecular subtypes of 247 TNBC patients in the TCGA and GEO databases based on the co-expression network genes, and survival differences and clinical characteristics were compared among different subtypes. Survival analysis was performed using the Kaplan-Meier method and log-rank test.

Eight cell types （epithelial cells， T cells， fibroblasts， macrophages， endothelial cells， tissue stem cells， B cells and common myeloid progenitor cells） were annotated in the GSE161529 dataset. Among them， six functionally distinct TAM subgroups were identified， which played roles in immune inflammation, energy metabolism and cell adhesion. In the GSE148673 dataset， high expression of TAM-related genes CLEC4E， CTSC， CTSH， and CTSS was associated with a favorable prognosis in TNBC patients （P<0.01）， while high expression of STAB1， RNASE1， SDS， SPP1 and TREM2 indicated a poor prognosis （P<0.01）. Through univariate Cox analysis and Pearson correlation analysis， a co-expression network of 26 TAM genes related to patient prognosis was constructed. TNBC patients were classified into protective type （Group A， 96 cases） and risky type （Group B， 99 cases） based on the expression of 26 TAM genes. The binary clustering heatmap showed high consistency within groups； the gene expression heatmap indicated that protective TAM genes were highly expressed in Group A and lowly expressed in Group B. Survival analysis showed that the overall survival of Group A patients was significantly better than that of Group B （χ²=6.63，P=0.010）； the clinical heatmap further revealed differences in age and clinical stage between two groups.

TAMs in breast cancer and its tumor microenvironment are heterogeneous， and six TAM subgroups have distinct roles in immune inflammation, energy metabolism and cell adhesion. TAM-related genes have clinical typing and prognostic prediction value in TNBC patients.