Examining Estrogen Receptor Mutations in ER+/HER2- Breast Cancer

Matthew P. Goetz, MD, discusses recent data on estrogen receptor mutations in patients with breast cancer.

Matthew P. Goetz, MD, consultant, Division of Medical Oncology, Department of Oncology, Mayo Clinic, discusses recent data on estrogen receptor (ER) mutations in patients with breast cancer.

According to Goetz, ER mutations are fairly new when examining hormonal therapy. During the 2022 European Society for Medical Oncology (ESMO) Congress, Goetz highlighted research on ER mutations by providing the results of the ELAINE 1 trial (NCT03781063).

ELAINE 1 evaluated the safety and efficacy of lasofoxifene vs fulvestrant (Faslodex) in patients with locally advanced/metastatic breast cancer and an estrogen receptor 1 mutation who progressed on aromatase and CDK 4/6 inhibitors.


0:08 | Estrogen receptor mutations are something that's relatively new in terms of the study of hormonal therapy. It's been thought for some time that these mutations might be present and indeed, the work done 20-30 years ago, when people looked at this, found that these mutations are very rare in the primary tumor, but they do occur and are selected, if you will, in the setting of ongoing hormonal therapy, in particular, aromatase inhibitors.

0:44 | These mutations confer ligand-independence. That means that the receptors constituently active, it signals and can induce the effects of what what otherwise would occur in the presence of the ligand, and that is the estrogen. One of the things that we know is that these mutations are a major driver of resistance to aromatase inhibitors. They occur fairly frequently, up to 30%-40% of the time in the metastatic setting.

1:17 | We also have emerging data that these mutations tend to confer a worse prognosis, especially those that have multiple mutations. This worse prognosis is clinically associated with higher rates of metastases. Certainly, therapeutic resistance, presents of visceral disease, and again, worse overall survival.