Purpose: This study reports the MTD, recommended phase 2 ose (RP2D), and preliminary efficacy of alpelisib or buparlisib used n combination with tamoxifen plus goserelin in premenopausal atients with hormone receptor–positive (HRþ), HER2-negative HER2) advanced breast cancer (ABC). Patients and Methods: This study enrolled premenopausal women with HRþ, HER2 ABC. Patients received tamoxifen (20 mg nce daily) and goserelin acetate (3.6 mg every 28 days) with either lpelisib (350 mg once daily; n ¼ 16) or buparlisib (100 mg once aily; n ¼ 13) in 28-day cycles until MTD was observed. Results: The criteria for MTD were not met for both alpelisib and uparlisib. The RP2D of alpelisib and buparlisib in combination with tamoxifen and goserelin were 350 mg and 100 mg, respectively. oth combinations met protocol-specified criteria for tolerability. The most common grade 3/4 treatment-emergent adverse events (TEAE) were hypokalemia (12.5%), hyperglycemia (6.3%), and rash (6.3%) for alpelisib and alanine aminotransferase increase (30.8%), aspartate aminotransferase increase (23.1%), and anxiety (15.4%) for buparlisib. TEAEs led to treatment discontinuation in 18.8% and 53.8% of alpelisib- and buparlisib-treated patients, respectively. Progression-free survival was 25.2 months in the alpelisib group and 20.6 months in the buparlisib group. Conclusions: The RP2Ds of alpelisib and buparlisib were 350 mg and 100 mg, respectively. No unexpected safety findings were reported. Although an early-phase study, data suggest that alpelisib plus endocrine therapy may be a potentially efficacious treatment that warrants further evaluation for premenopausal patients with HRþ, HER2 ABC.