Autophagy is a cellular process that helps maintain homeostasis during metabolic stress by degrading damaged organelles and proteins. However, excessive autophagy can lead to cell death. In mammary tumorigenesis, autophagy acts as a tumor suppressor, as the essential autophagy regulator beclin1 is monoallelically deleted in breast cancers. This study shows that allelic loss of beclin1 and defective autophagy make mammary epithelial cells more susceptible to metabolic stress, leading to DNA damage and genomic instability, which promote breast cancer progression. Autophagy defects also activate the DNA damage response, promote gene amplification, and synergize with defective apoptosis to accelerate mammary tumorigenesis. The study demonstrates that autophagy limits metabolic stress and protects the genome, while defective autophagy increases DNA damage and genomic instability, facilitating breast cancer progression. The findings suggest that autophagy plays a dual role in both cell survival and tumor suppression, and that defective autophagy may be a key factor in breast cancer development. The study also highlights the importance of autophagy in maintaining cellular homeostasis and preventing genomic instability in mammary epithelial cells. The results have important implications for the development of therapeutic strategies targeting autophagy in breast cancer.Autophagy is a cellular process that helps maintain homeostasis during metabolic stress by degrading damaged organelles and proteins. However, excessive autophagy can lead to cell death. In mammary tumorigenesis, autophagy acts as a tumor suppressor, as the essential autophagy regulator beclin1 is monoallelically deleted in breast cancers. This study shows that allelic loss of beclin1 and defective autophagy make mammary epithelial cells more susceptible to metabolic stress, leading to DNA damage and genomic instability, which promote breast cancer progression. Autophagy defects also activate the DNA damage response, promote gene amplification, and synergize with defective apoptosis to accelerate mammary tumorigenesis. The study demonstrates that autophagy limits metabolic stress and protects the genome, while defective autophagy increases DNA damage and genomic instability, facilitating breast cancer progression. The findings suggest that autophagy plays a dual role in both cell survival and tumor suppression, and that defective autophagy may be a key factor in breast cancer development. The study also highlights the importance of autophagy in maintaining cellular homeostasis and preventing genomic instability in mammary epithelial cells. The results have important implications for the development of therapeutic strategies targeting autophagy in breast cancer.