In this study, we performed integrated multi-omics analyses using genomic (n = 79), transcriptomic (n = 42), proteomic (n = 224), and phosphoproteomic (n = 49) data collected from 224 samples from 168 patients with malignant and benign breast diseases. Our data revealed the characteristics of the linear multi-step progression of BRDC and provided a resource to explore the temporal order of a series of biological events in the progression of BRDC. In addition, we identified potential therapeutic agents, aspirin and dydrogesterone, that target AKR1C1 and demonstrated their inhibitory effect on tumor cells. In summary, our study helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.