Activating PIK3CA mutations are the most frequent genomic alterations in oestrogen receptor (ER)-positive breast cancers and PI3K inhibition results in increased expression of ESR1 mRNA and ER protein together with enhanced ER-driven transcriptional activity, with these effects seen in laboratory models and in tumours from patients treated with the PI3Kα-specific inhibitor BYL719 [57]. The gene discussed is PIK3CG; the disease is breast cancer.