Because breast tumor tissues were not available for metabolomic analysis we cannot discard the possibility that, beyond an indirect effect of metformin on hepatic and adipose tissues and perhaps also on short-chain fatty acid (butyrate-producing gut microbiota [40,41], it could directly promote inhibition of the mTOR pathway and increase fatty acid oxidation in the breast cancer tumor cells themselves, altogether contributing to the apparent release of BHBA into the serum of HER2-positive breast cancer patients co-treated with metformin. This evidence concerns the gene ERBB2 and breast carcinoma.