These results suggest that, in normal mammary tissue, the LCn-3 PUFA, through their ability to maintain the ERK1/2 and PI3K/Akt/mTOR at low level of activities, could have the potential to exert a preventive action against the risk of breast cancer, comparable to that of selective estrogen receptor modulators, now approved for breast cancer prevention (Tamoxifen and Raloxifene). This evidence concerns the gene PIK3CA and breast cancer.