Abstract
BACKGROUND: Breast cancer remains one of the most common and lethal malignancies among women. Despite advanced targeted therapies and precision medicine, therapeutic resistance continues to undermine durable clinical responses. Increasing evidence links epigenetic dysregulation and autophagy as central contributors to breast cancer progression, therapy resistance, and metabolic changes. Histone modifications, non-coding RNAs, and DNA methylation dynamically regulate autophagy-related genes (ATGs), while autophagy itself co-regulates the epigenetic landscape under chemotherapeutic stress. This two-way interplay determines tumor cell fate, influencing sensitivity to chemotherapy, endocrine therapy, and targeted agents. AIMS: This article reviews recent studies on epigenetic mechanisms modulating autophagy and their impact on resistance pathways in breast cancer. Furthermore, this article highlighted the emerging role of epigenetic-autophagy as a biomarker for early detection, disease monitoring, and predicting therapeutic response. CONCLUSION: Finally, the review outlined new therapeutic methods that combine epigenetic modulators and autophagy inhibitors with particular attention to AI-driven drug discovery and precision oncology. Collectively, this review emphasizes the potential of targeting epigenetic-autophagy crosstalk to overcome therapy resistance and improve patient outcomes.