ESR1 mutations are different from other mutations in mBC1-7
ESR1 mutations can emerge during 1L treatment with ET, resulting in faster disease progression and poorer outcomes for patients1,2
ESR1 mutations may have emerged during 1L treatment and now may be the driver of disease progression1,2
*Based on treatment with AI therapy.
The unmet need in ESR1-mutated, ER+/HER2- mBC
In ER+/HER2- mBC
SERMs and fulvestrant have decreased binding affinity for ESR1-mutated receptors1
Adapted with permission from Brett JO, Spring LM, Bardia A, Wander SA. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85.
†Specifically refers to tamoxifen from this analysis.
- ESR1 mutations stabilize the active conformation in the absence of ligand, reducing their affinity for ligands, including estrogen, SERMs, and SERDs1
Abbreviations: 1L, first line; ER+, estrogen receptor-positive; ESR1, estrogen receptor 1; ESR1m, estrogen receptor 1 mutation; ET, endocrine therapy; HER2-, human epidermal growth factor receptor 2-negative; mBC, metastatic breast cancer; SERDs, selective estrogen receptor degraders; SERMs, selective estrogen receptor modulators.
References: 1. Brett JO, Spring LM, Bardia A, et al. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. Breast Cancer Res. 2021;23(1):85. 2. Zhang K, Hong R, Xu F, et al. Clinical value of circulating ESR1 mutations for patients with metastatic breast cancer: a meta-analysis. Cancer Manag Res. 2018;10:2573-2580. 3. Mankoo PK, Sukumar S, Karchin R. PIK3CA somatic mutations in breast cancer: mechanistic insights from Langevin dynamics simulations. Proteins. 2009;75(2):499-508. 4. Casaubon JT, Kashyap S, Regan JP. BRCA1 and BRCA2 Mutations. In: StatPearls. Treasure Island (FL): StatPearls Publishing; 2023. 5. Arthur LM, Turnbull AK, Renshaw L, et al. Changes in PIK3CA mutation status are not associated with recurrence, metastatic disease or progression in endocrine-treated breast cancer. Breast Cancer Res Treat. 2014;147(1):211-219. 6. Clatot F, Perdrix A, Beaussire L, 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. 7. Turner NC, Swift C, Kilburn L, et al. ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor-positive breast cancer: a combined analysis of the phase III SoFEA and EFECT trials. Clin Cancer Res. 2020;26(19):5172-5177.