Despite major therapeutic advances, breast cancer remains the primary cause of cancer-related mortality among women. Substantial unmet needs remain, particularly with regard to patients with early-stage breast cancer who are at increased risk of recurrence. This is highly evident in patients with breast cancer that is hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-). The HR+/HER- breast cancer subtype is the most common, and about 20% to 30% of patients with HR+/HER2- early breast cancer (EBC) will experience a recurrence within 5 years of follow-up; furthermore, patients with disease exhibiting certain high-risk clinical-pathological features are more likely to experience recurrence. The treatment paradigm for these patients has changed significantly with the availability of CDK4/6 inhibitor-based therapy indicated for HR+/HER2- EBCs at high risk of recurrence. However, clinicians are often unclear on the optimal use of these therapies in practice. In this activity, expert faculty review the importance of assessing risk of recurrence in early-stage ER+/HER2- breast cancer, the supporting data for currently available therapies in this setting, and strategies to monitor and manage adverse events related to these agents. During the fireside chat, attendees with have the opportunities to share their own experiences and best practices for optimizing CDK4/6 inhibitors in the daily clinic.