Novartis receives Food and Drug Administration (FDA) Breakthrough Therapy (BT) designation for ribociclib (Kisqali), an initial endocrine-based treatment of pre- or perimenopausal women with hormone-receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2–) advanced or metastatic breast cancer (mBC) in combination with tamoxifen or an aromatase inhibitor (AI). This BT designation is based on positive results of the phase III MONALEESA-7 trial demonstrating that ribociclib in combination with tamoxifen or an AI as initial endocrine-based therapy significantly prolonged progression-free survival (PFS) compared with endocrine therapy alone (median PFS = 23.8, [95% CI: 19.2 months, not reached] vs 13.0 months [95% CI: 11.0–16.4 months]; HR = 0.553; 95% CI: 0.441–0.694; P <.0001). MONALEESA-7 is the first phase III trial entirely dedicated to evaluating a cyclin D-dependent kinase 4/6 inhibitor in premenopausal women with HR+/HER2– advanced breast cancer. In subgroup analyses of median PFS by endocrine partner, ribociclib in combination with tamoxifen and goserelin demonstrated 22.1 months median PFS compared with 11.0 months for tamoxifen and goserelin alone; ribociclib in combination with an AI and goserelin demonstrated 27.5 months median PFS compared with 13.8 months for an AI and goserelin alone. No new safety signals were observed in the MONALEESA-7 trial; adverse events (AEs) were generally consistent with those observed in MONALEESA-2, identified early, and mostly managed through dose interruptions or reductions. The most common (≥5%) grade 3/4 AEs in patients receiving ribociclib combination therapy compared with endocrine therapy alone were neutropenia (60.6% vs 3.6%) and leucopenia (14.3% vs 1.2%). This is the second BT designation granted to ribociclib for initial endocrine-based treatment in HR+/HER2– advanced or mBC.