Esr1, the estrogen receptor 1 gene, encodes the estrogen receptor alpha protein. Estrogen receptors play a crucial role in mediating the effects of estrogen, a key hormone in the body. This gene is involved in numerous biological processes such as cell growth, differentiation, and metabolism, and is also closely associated with endocrine-related signaling pathways. Its significance extends to many physiological and pathological conditions, especially those related to hormone-dependent tissues and diseases [1,2,3,4,5,6].

In breast cancer, acquired ligand-independent ESR1 mutations during aromatase inhibitor therapy in metastatic estrogen receptor-positive breast cancer are a common mechanism of hormonal therapy resistance. These mutations can preexist in primary tumors and be enriched during metastasis, expressing a unique transcriptional profile that favors tumor progression [1]. In metastatic hormone receptor-positive breast cancer, ESR1 mutations are a common cause of acquired resistance to estrogen deprivation by aromatase inhibition. For estrogen receptor-targeting therapies like tamoxifen and fulvestrant, ESR1 mutations cause relative resistance in vitro, but not clearly in patients. Regarding combination therapies, ESR1 mutations nullify the aromatase inhibitor component [3]. Liquid biopsy, especially analysis of circulating tumor DNA, has emerged as a promising way to identify ESR1 mutations, with digital droplet PCR excelling in detecting hotspot mutations and next-generation sequencing offering comprehensive coverage of ESR1 mutations [2].

In summary, Esr1 is essential for mediating estrogen-related functions. In the context of breast cancer, research using in-vivo models (implied by the study of its role in disease) has shown that ESR1 mutations are a significant factor in endocrine therapy resistance. Understanding Esr1 and its mutations through such model-based research provides insights into developing more effective treatment strategies for hormone-receptor-positive breast cancers [1,2,3,4,5,6].

References:

1. Dustin, Derek, Gu, Guowei, Fuqua, Suzanne A W. 2019. ESR1 mutations in breast cancer. In Cancer, 125, 3714-3728. doi:10.1002/cncr.32345. https://pubmed.ncbi.nlm.nih.gov/31318440/

2. Venetis, Konstantinos, Pepe, Francesco, Pescia, Carlo, Fusco, Nicola, Malapelle, Umberto. 2023. ESR1 mutations in HR+/HER2-metastatic breast cancer: Enhancing the accuracy of ctDNA testing. In Cancer treatment reviews, 121, 102642. doi:10.1016/j.ctrv.2023.102642. https://pubmed.ncbi.nlm.nih.gov/37864956/

3. Brett, Jamie O, Spring, Laura M, Bardia, Aditya, Wander, Seth A. 2021. ESR1 mutation as an emerging clinical biomarker in metastatic hormone receptor-positive breast cancer. In Breast cancer research : BCR, 23, 85. doi:10.1186/s13058-021-01462-3. https://pubmed.ncbi.nlm.nih.gov/34392831/

4. Carausu, Marcela, Bidard, François-Clément, Callens, Celine, Pierga, Jean-Yves, Cabel, Luc. 2019. ESR1 mutations: a new biomarker in breast cancer. In Expert review of molecular diagnostics, 19, 599-611. doi:10.1080/14737159.2019.1631799. https://pubmed.ncbi.nlm.nih.gov/31188645/

5. Nagy, Zsuzsanna, Jeselsohn, Rinath. 2023. ESR1 fusions and therapeutic resistance in metastatic breast cancer. In Frontiers in oncology, 12, 1037531. doi:10.3389/fonc.2022.1037531. https://pubmed.ncbi.nlm.nih.gov/36686845/

6. Betz, Margaux, Massard, Vincent, Gilson, Pauline, Harlé, Alexandre, Merlin, Jean-Louis. 2023. ESR1 Gene Mutations and Liquid Biopsy in ER-Positive Breast Cancers: A Small Step Forward, a Giant Leap for Personalization of Endocrine Therapy? In Cancers, 15, . doi:10.3390/cancers15215169. https://pubmed.ncbi.nlm.nih.gov/37958343/