RB1 and breast cancer: We also observed increased frequencies of genomic alterations at PD for BC genes such as BRCA1/2 and TP53 and notably a high prevalence of acquired alterations affecting ESR1, RB1, KMT2C, and PTEN. Mutations affecting the histone methyltransferase gene KMT2C are frequent in ER-positive BC, and KMT2C loss has been associated with a poor prognosis in patients on ET [48].