Clinical Implications and Treatment Strategies for ESR1 Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series

In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive act...

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Published in:The oncologist (Dayton, Ohio) Ohio), 2023-02, Vol.28 (2), p.172-179
Main Authors: Brett, Jamie O, Ritterhouse, Lauren L, Newman, Erik T, Irwin, Kelly E, Dawson, Megan, Ryan, Lianne Y, Spring, Laura M, Rivera, Miguel N, Lennerz, Jochen K, Dias-Santagata, Dora, Ellisen, Leif W, Bardia, Aditya, Wander, Seth A
Format: Article
Language:English
Subjects:
Antimitotic agents
Antineoplastic agents
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Care and treatment
Development and progression
Diagnosis
Dosage and administration
Drug Resistance, Neoplasm - genetics
Estrogen
Estrogen Receptor alpha - genetics
Female
Gene mutations
Genes
Genetic aspects
Health aspects
Hormone therapy
Hormones
Humans
Metastasis
Mutation
Patient outcomes
Precision Medicine Clinic: Molecular Tumor Board
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Summary:In hormone receptor-positive metastatic breast cancer (HR+ MBC), endocrine resistance is commonly due to genetic alterations of ESR1, the gene encoding estrogen receptor alpha (ERα). While ESR1 point mutations (ESR1-MUT) cause acquired resistance to aromatase inhibition (AI) through constitutive activation, far less is known about the molecular functions and clinical consequences of ESR1 fusions (ESR1-FUS). This case series discusses 4 patients with HR+ MBC with ESR1-FUS in the context of the existing ESR1-FUS literature. We consider therapeutic strategies and raise the hypothesis that CDK4/6 inhibition (CDK4/6i) may be effective against ESR1-FUS with functional ligand-binding domain swaps. These cases highlight the importance of screening for ESR1-FUS in patients with HR+ MBC while continuing investigation of precision treatments for these genomic rearrangements.
ISSN:1083-7159
1549-490X
DOI:10.1093/oncolo/oyac248