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The oncometabolite, D-2-hydroxyglutarate, accumulates in various cancers because of acquired mutations in isocitrate dehydrogenase 1 & 2. Here, we describe a new mechanism for D-2-hydroxyglutarate accumulation in breast cancer. It involves c-Myc signaling and alcohol dehydrogenase, iron-containing protein 1 (ADHFE1) and leads to metabolic reprogramming, de-differentiation, and increased mammary tumorigenesis.