Using the clonal breast cancer cell line MCF10DCIS.com, which harbors the gain-of-function H1047R hot-spot mutation in the catalytic domain of the PI3KCA gene and has been shown to form DR-refractory xenotumors [8], and taking advantage of the isogenic conversion of a wild-type tumor into a PIK3CA H1047R-mutated tumor using the highly metastatic SW48 colorectal cancer cell line, we have shown that metformin can no longer be considered a bona fide DR mimetic, at least in terms of anti-cancer activity. The gene discussed is PIK3CA; the disease is breast cancer.