mBC tumors acquire ESR1m directly under pressure from prior ET, primarily AI1
Unlike PIK3CA/AKT/PTEN mutations that may not have been treated since mBC diagnosis, ESR1m are acquired at progression3-8
In ER+/HER2- mBC
SERMs and fulvestrant have decreased binding affinity for ESR1-mutated receptors3
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 SERDs3
ESR1 mutations are a biomarker for resistance to ET, such as AI and fulvestrant3
Abbreviations: AI, aromatase inhibitor; AKT, protein kinase B; 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; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN, phosphatase and tensin homolog; SERDs, selective estrogen receptor degraders; SERMs, selective estrogen receptor modulators.
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