Conferences / ASCO 06/11/2026

How To Approach Endocrine Therapies for Metastatic Breast Cancer in the Adjuvant CDK4/6 Inhibitor Era

A smiling Asian woman with long black hair wearing a white blazer and blue top, standing in front of a bright window with greenery outside, representing healthcare professionals in oncology research. Jasmin Hundal, MD High-quality medical professional woman smiling, representing oncology and cancer treatment awareness for OncUpdates website. Dionisia Quiroga, DO, PhD

Key Points

  • CDK4/6 inhibitor plus aromatase inhibitor combinations are the standard of care first-line therapy for hormone receptor (HR)–positive breast cancer.
  • Subsequent endocrine therapies may still be effective in aromatase inhibitor–exposed patients depending on prior response, progression characteristics, and time since adjuvant therapy.
  • Opting for chemotherapy or other treatments may be more effective in patients who show resistance to endocrine therapies.

Jasmin Hundal, MD, MS, MPH, oncology fellow at Cleveland Clinic, and Dionisia Quiroga, DO, PhD, FASCO, assistant professor at The Ohio State University, spoke about the nuances emerging around endocrine therapies in patients with HR–positive breast cancer. 

For first-line, adjuvant treatment of HR–positive breast cancer, current data support one of two approved CDK4/6 inhibitor and aromatase inhibitor combinations as the standard of care. However, as these regimens have been adopted and as novel endocrine therapies have been developed, selecting later-line treatments has become more complex. 

In CDK4/6 inhibitor and aromatase inhibitor–exposed patients, the National Comprehensive Cancer Network guidelines recommend abemaciclib plus imlunestrant as a potential follow-up therapy. However, only single-agent imlunestrant is currently approved by the FDA. Dr. Quiroga felt that the abemaciclib plus imlunestrant combination is a viable option, particularly in patients who had a durable response to first-line therapy and showed limited disease progression.

The timing of disease progression may also impact treatment selection for metastatic disease. Data have shown that patients who progress while on endocrine therapy, with or without a CDK4/6 inhibitor, are more likely to be endocrine-resistant and have aggressive disease biology. Opting for chemotherapy or other treatment strategies instead of additional endocrine therapies may be more appropriate for these patients, said Dr. Quiroga.