Breast cancer (BRCA) is a common malignancy worldwide that is associated with a high mortality rate. Despite recent improvements in diagnosis and treatment, there is an urgent need to investigate the processes underlying cancer progression and identify novel prognostic indicators. Anoikis, which plays a role in the development of human malignant tumors, has been gaining increasing interest from researchers. However, the potential role of anoikis-related genes (ANRGs) in the advancement of BRCA remains unknown. In this study, we aimed to assess the predictive value of ANRGs in BRCA, construct a prognostic model based on ANRGs, and explore the tumor microenvironment in different prognostic score groups. This study utilized data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to collect clinical information and RNA sequencing data from patients with BRCA. Information on ANRGs was gathered from GeneCards and Harmonizome portals. A risk score model based on ANRGs was created using least absolute shrinkage and selection operator Cox (LASSO) regression analysis. Additionally, the study explored the tumor microenvironment and enriched pathways in different risk groups. Finally, a novel ANRG-based nomogram is developed. A total of 142 differentially expressed genes associated with survival were identified, of which 5 genes were selected to create the ANRG signature. The risk score based on this signature proved to be an independent prognostic factor. Further analysis revealed that different risk subgroups exhibited variations in the tumor microenvironment and drug sensitivities. Subsequently, a nomogram was developed using risk scores and clinicopathological factors. The decision curve analysis results suggest that patients with BRCA might derive clinical treatment benefits from utilizing this prognostic model. Based on the results of this study, the ANRG signature and nomograph established can be used for clinical decision-making in patients with BRCA.