Immune checkpoint blockade, an immunotherapy, has been applied in multiple systemic malignancies and has improved overall survival to a relatively great extent; whether it can be applied in breast cancer remains unknown. We endeavored to explore possible factors that may influence immunotherapy outcomes in breast cancer using several public databases. The possible treatment target TNF superfamily member 4 (TNFSF4) was selected from many candidates based on its abnormal expression profile, survival-associated status, and ability to predict immune system reactions. For the first time, we identified the oncogenic features of TNFSF4 in breast carcinoma. TNFSF4 was revealed to be closely related to treatment that induced antitumor immunity and to interact with multiple immune effector molecules and T cell signatures, which was independent of endocrine status and has not been reported previously. Moreover, the potential immunotherapeutic approach of TNFSF4 blockade showed underlying effects on stem cell expansion, which more strongly and specifically demonstrated the potential effects of applying TNFSF4 blockade-based immunotherapies in breast carcinomas. We identified potential targets that may contribute to breast cancer therapies through clinical analysis and real-world review and provided one potential but crucial tool for treating breast carcinoma that showed effects across subtypes and long-term effectiveness.