Not only does this provide another independent validation of the biological significance of our AKT gene module, but also provides a means of identifying ER+ breast cancer patients who do not respond well to endocrine therapy and who instead may benefit from additional treatment targeting the AKT/mTOR signaling axis, independently of whether key genomic or epigenomic alterations are present in this pathway or not. The gene discussed is ESR1; the disease is breast carcinoma.