Erica Mayer, MD, and Kelly McCann, MD, outline how clinicians define high-risk hormone receptor–positive, HER2-negative early breast cancer in contemporary practice.

Long-term follow-up from the monarchE and NATALEE trials continues to influence treatment decisions in HR-positive, HER2-negative early breast cancer.

A premenopausal patient with stage III, node-positive HR-positive, HER2-negative breast cancer is presented to illustrate real-world risk stratification.

Using the same high-risk patient scenario, the discussion turns to practical strategies for sequencing adjuvant endocrine therapy, ovarian function suppression, and CDK4/6 inhibition.

Treatment selection between abemaciclib and ribociclib is explored for a patient with extensive nodal involvement.

Strategies to improve tolerability and adherence to abemaciclib in the adjuvant setting are examined in detail.

Strategies to improve tolerability and adherence to abemaciclib in the adjuvant setting are examined in detail.

A second case highlights a postmenopausal patient with lower nodal burden but biologically high-risk HR-positive, HER2-negative breast cancer.

Looking ahead, the faculty discuss unanswered questions and future data needs in the adjuvant treatment of HR-positive, HER2-negative early breast cancer.