ESR1 Mutations Are Not a Common Mechanism of Endocrine Resistance in Patients With Estrogen Receptor –Positive Breast Cancer Treated With Neoadjuvant Aromatase Inhibitor Therapy

In this study, we evaluated the prevalence of ESR1m in tumor samples from patients with ER+ breast cancer resistant to neoadjuvant aromatase inhibitor therapy.Methods: We followed a prospective cohort of patients with ER+ HER2– stages II and III breast cancer treated with neoadjuvant endocrine therapy (NET). Tumor samples from patients with a pattern of primary endocrine resistance [defined as a Preoperative Endocrine Prognostic Index (PEPI) score of ≥4] were identified and analyzed for the presence of ESR1m.Results: One hundred twenty-seven patients were included in the cohort, of which 100 (79%) had completed NET and underwent surgery. Among these patients, the PEPI score ranged from 0 to 3 in 70% (70/100), whereas 30% (30/100) had a PEPI score of 4 or more. Twenty-three of these patients were included in the analysis. ESR1 mutations were not identified in any of the 23 patients with early-stage ER+ breast cancer resistant to NET.Discussion: Growing evidence supports the notion that there are different mechanisms for primary and secondary endocrine resistance. Our study suggests that ESR1 mutations do not evolve rapidly and do not represent a common mechanism of primary endocrine resistance in the neoadjuvant setting. Therefore, ESR1m should be considered a mechanism of acquired endocrine resistance in the context of advanced disease. Further research should be conducted to identify factors associated with intrinsic resistance to ET.
Source: Frontiers in Oncology - Category: Cancer & Oncology Source Type: research