TNFRSF1A and breast neoplasm: 19. Transcriptome profiling of breast tumors pre- and postmetformin treatment found that metformin downregulated phosphodiesterase 3B, a critical regulator of cAMP levels that also regulates activation of AMPK 18. Metformin was also found to have significant effects on the tumor necrosis factor receptor-1, mTOR, AMPK, p53, BRCA1, and cell cycle pathways 18.