Endocrine resistance will eventually develop in patients with ER-positive breast cancer receiving endocrine therapy. Several studies unveiled gain-of-function mutations in theESR1 gene in approximately 20% of patients with metastatic ER-positive disease who received endocrine therapies. These mutations lead to ligand-independent ER activity that promotes tumour growth, partial resistance to endocrine therapy, and potentially enhanced metastatic capacity. We discuss the contribution of ESR1mutations to the development of acquired endocrine resistance, and evaluate how mutated ER can be detected and targeted to overcome resistance and improve patient outcomes.
- Rinath Jeselsohn
- Gilles Buchwalter
- Rachel Schiff
