The phase 3 NSABP B-59/GeparDouze trial, in which patients with early-stage triple-negative breast cancer received neoadjuvant chemotherapy with or without atezolizumab, did not meet its primary endpoint of event-free survival, and comprehensive translational analyses show tumor microenvironment-dependent determinants of response, with basal-like immune-activated tumors potentially responding to atezolizumab and chemotherapy.