This content is sponsored by AstraZeneca.
Download Slides
To help patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2–) advanced breast cancer have the best chance of extending the benefit of first-line (1L) aromatase inhibitor plus cyclin-dependent kinase 4/6 (CDK4/6) inhibitor regimens, it may be critical to detect emerging endocrine resistance as early as possible.1-3 As exposure to aromatase inhibitors increases, Estrogen Receptor 1 (ESR1) mutations may emerge and signal clinical progression, greater tumor complexity, and shorter progression-free and overall survival.4-8 Join Seth Wander as he reviews evidence supporting earlier intervention and discusses the potential role of monitoring for emerging ESR1 mutations during 1L endocrine treatment. Wander is a medical oncologist at Massachusetts General Hospital; Director of Translational Research in the Breast Oncology Program; Director of Precision Medicine at the Termeer Center for Targeted Therapies, Massachusetts General Hospital; and Assistant Professor of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
Learning Objectives:
- The emergence of ESR1 mutations during 1L therapy for HR+/HER2– advanced breast cancer and how they may contribute to endocrine resistance
- The potential impact of monitoring for ESR1 mutations through circulating tumor DNA (ctDNA) blood testing during 1L therapy to identify emerging endocrine resistance
- Why earlier identification of endocrine resistance might allow clinicians to personalize or adjust treatment before overt disease progression occurs
Speaker:
Seth Wander1
1. Medical Oncologist; Director of Translational Research, Breast Oncology Program, Massachusetts General Hospital; Director of Precision Medicine, Termeer Center for Targeted Therapies; Assistant Professor of Medicine, Harvard Medical School, Boston, Massachusetts, USA
References:
1. Bidard FC et al. Switch to fulvestrant and palbociclib versus no switch in advanced breast cancer with rising ESR1 mutation during aromatase inhibitor and palbociclib therapy (PADA-1): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol. 2022;23(11):1367-77.
2. Living Beyond Breast Cancer. Metastatic breast cancer to the bones. Available at: https://www.lbbc.org/about-breast-cancer/types-breast-cancer/metastatic-breast-cancer/bone-metastases. Last accessed: January 12, 2026.
3. Living Beyond Breast Cancer. Testing and precision medicine. Available at: https://www.lbbc.org/about-breast-cancer/testing. Last accessed: January 12, 2026.
4. Brett JO et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85.
5. Allouchery V et al. Circulating ESR1 mutations at the end of aromatase inhibitor adjuvant treatment and after relapse in breast cancer patients. Breast Cancer Res. 2018;20(1):40.
6. Bhave MA et al. Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice. Breast Cancer Res Treat. 2024;207(3):599-609.
7. Clatot F et al. Risk of early progression according to circulating ESR1 mutation, CA-15.3 and cfDNA increases under first-line anti-aromatase treatment in metastatic breast cancer. Breast Cancer Res. 2020;22(1):56.
8. Meisel JL et al. Real-world treatment patterns and clinical outcomes in patients with emerging estrogen receptor 1 (ESR1)-mutated ER+ metastatic breast cancer in the U.S., 2018-2024. Poster PS2-02-04. SABCS 2025, December 9-12, 2025.
©2026 AstraZeneca. All rights reserved. US-115628 Last Updated 10/26
