Within the I-SPY 2 study evaluating the effect of neoadjuvant therapy with an AKT inhibitor in 84 high risk early BC patients, the ctDNA clearance from baseline to three weeks after therapy initiation was related to an increased pCR rate (48% pCR compared to 17% pCR in patients with ctDNA after three weeks) and ctDNA presence after 3 weeks under therapy was significantly associated with increased risk of metastatic recurrence (HR 4.5; 95% CI 1.2–17.4) [122]. This evidence concerns the gene AKT1 and breast cancer.