Dr. Goetz on Treatment Challenges for ESR1-Mutant Breast Cancer

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses the treatment landscape of estrogen receptor (ER)—positive breast cancer and advances made within the last 5 years.

The landscape for the treatment of ER-positive breast cancer has changed dramatically, especially within the last 5 years, explains Goetz. However, resistance to endocrine therapy can emerge in patients who have been previously treated with tamoxifen and responded well for a period of time. One of the mechanisms for resistance that has been identified is the emergence of ESR1 mutations. These mutations are present in about 30% to 40% of patients who have been treated with hormonal therapy, according to Goetz, and appear to be an acquired resistance mechanism. The presence of these mutations has created worse prognoses for patients with ER-resistant breast cancer.

However, physicians are beginning to learn about new ways to treat these patients. In the past 5 years, agents that have become available are CDK4/6 inhibitors.

The problem, according to Goetz, is that the best treatment after progression for patients with ESR1-mutant breast cancer who have received prior treatment with a CDK4/6 inhibitor is unknown. Goetz also wonders what the optimal hormonal drug is that should be combined with CDK4/6 inhibitors to serve patients with ESR1 mutations.