A total of 1034 patients were recruited into four treatment cohorts, based on mutations identified in ctDNA—cohort A, with ESR1 mutations treated with extended dose of fulvestrant; cohort B, with HER2 mutations received oral neratinib and in case of ER+ breast cancer with a standard-dose of fulvestrant; cohort C, with AKT1 mutations in ER+ cancer treated with capivasertib + standard-dose of fulvestrant; and corhort D, with AKT1 mutations in ER- cancer or with PTEN mutations treated with capivasertib [146]. This evidence concerns the gene ESR1 and breast cancer.