Clinical Implications and Treatment Strategies for <i>ESR1</i> Fusions in Hormone Receptor-Positive Metastatic Breast Cancer: A Case Series
Jamie O. Brett, Lauren L. Ritterhouse, Erik T. Newman, Kelly Irwin, Megan Dawson, Lianne Ryan, Laura M. Spring, Miguel N. Rivera, Jochen K. Lennerz, Dora Dias‐Santagata, Leif W. Ellisen, Aditya Bardia, Seth A. Wander
Abstract
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.