A Phase III Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating The Efficacy And Safety Of GDC-9545 Combined With PALBOCICLIB Compared With LETROZOLE Combined With PALBOCICLIB In Patients With ESTROGEN RECEPTOR-POSITIVE, HER2-NEGATIVE Locally Advanced Or Metastatic Breast Cancer. The target patient population for this study is women and men with previously untreated, ER-positive, HER2-negative locally advanced (recurrent or progressed) or metastatic breast cancer. Both postmenopausal and premenopausal/perimenopausal women will be included in the study. Premenopausal/perimenopausal women will receive LHRH agonists for ovarian function suppression. The population described by the eligibility criteria reflects patients for whom the combination of palbociclib and letrozole represents an appropriate standard-of-care therapy.