RARA and breast cancer: DNA hypermethylation of transcriptionally repressed RARA-target genes, which is interpreted as functional inhibition of RARA transcriptional activity [40, 61, 62], or AKT phosphorylation (P-AKT), which is interpreted as aberrant activation of PI3K kinase [63], were found in early stages breast cancer, even before evidence of breast cancer in mammograms [61].