title: ESR1 mutations: Moving towards guiding treatment decision-making in metastatic breast cancer patients.
abstract: Mutations in the gene coding for the estrogen receptor (ER), ESR1, have been associated with acquired endocrine resistance in patients with ER-positive metastatic breast cancer (MBC). Functional studies revealed that these ESR1 mutations lead to constitutive activity of the ER, meaning that the receptor is active in absence of its ligand estrogen, conferring resistance against several endocrine agents. While recent clinical studies reported that the occurrence of ESR1 mutations is rare in primary breast cancer tumors, these mutations are more frequently observed in metastatic tissue and circulating cell-free DNA of MBC patients pretreated with endocrine therapy. Given the assumed impact that the presence of ESR1 mutations has on outcome to endocrine therapy, assessing ESR1 mutations in MBC patients is likely to be of significant interest to further individualize treatment for MBC patients. Here, ESR1 mutation detection methods and the most relevant pre-clinical and clinical studies on ESR1 mutations regarding endocrine resistance are reviewed, with particular interest in the ultimate goal of guiding treatment decision-making based on ESR1 mutations.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands. Electronic address: l.angus@erasmusmc.nl.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Angus
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Nick
authors.initials: N
authors.lastname: Beije
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: John W M
authors.initials: JW
authors.lastname: Martens
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Sleijfer
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis / Q000379:methods; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D006801:Humans; D009154:Mutation; D009362:Neoplasm Metastasis
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha
keywords: Cell-free DNA; ESR1 mutations; Endocrine resistance; Metastatic breast cancer