ESR1 and breast cancer: Clinical trials BELLE-3 of pan-PI3K inhibitor buparlisib with ESR1 antagonist fulvestrant in patients with HR+/HER2− advanced or metastatic BCs showed statistically significantly longer progression-free survival (PFS) in the treatment group vs. placebo; however, due to high rates of grade 3–4 adverse events, further development of buparlisib in BC was halted [19,20].