PIK3CA and breast cancer: While a recent phase 2 study using MK-2206 and anastrozole in PIK3CA-mutant ER-positive breast cancer did not show additive efficacy [37], alpelisib in combination with fulvestrant received FDA approval for the treatment of patients with PIK3CA-mutated HR+ advanced breast cancer after previous endocrine therapy (PFS 11.0 versus 5.7 months) and also showed a treatment benefit in patients without PIK3CA mutation compared to placebo control (overall response rate 26.6% versus 12.8%) [38].