Dr. Ellis on Resistance to Endocrine Therapy in HR+ Metastatic Breast Cancer

Matthew J. Ellis, MD, PhD, professor and director, Lester and Sue Smith Breast Center, associate director of precision medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, discusses resistance to endocrine therapy in hormone receptor (HR)-positive breast cancer.

Resistance to endocrine therapy is one of the biggest problems in the treatment of patients with HR-positive breast cancer. Most patients with HR-positive breast cancer will experience resistance at some point in their duration of treatment. This may be during the first few months of therapy or at progression 3 to 5 years down the line, says Ellis.

There are 2 types of resistance, states Ellis—intrinsic resistance and acquired resistance. Researchers have studied the molecular biology of acquired resistance to endocrine therapy and found that recurring events within the estrogen receptor (ER) gene itself are a cause of acquired resistance in as many as 40% of patients.

ER translocations are another recoding event. When those events occur, says Ellis, all endocrine therapy becomes obsolete because there is nowhere for the drug to bind to. However, experimental systems and patients who have mutations or fusions have shown responses to CDK4/6 inhibitors, explains Ellis.