Loss of luminal lineage drives resistance to next-generation ERα antagonists in pretreated ER+ HER2− locally-advanced or metastatic breast cancer

Nature Communications 2026 Open access

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Authors: Jackson Liang, Christy C. Ong, Kareem A. Heslop, Jane Guan, Vasumathi Kameswaran, Bence Dániel, Minyi Shi, Yuxin Liang, Jennifer M. Giltnane, Junko Aimi, Ching-Wei Chang, Mary Gates
+7 more Jennifer Eng-Wong, Pablo Perez-Moreno, Komal L. Jhaveri, N. C. Turner, Elgene Lim, Ciara Metcalfe, Heather M. Moore
DOI: 10.1038/s41467-026-71233-1
Cited by: 2
References: 54

Abstract

Abstract Next-generation selective estrogen receptor-α (ERα) antagonist/degraders (SERDs) are being developed for ER-positive breast cancer (ER + BC), with intentions of improving outcomes for patients. In recent clinical trials of metastatic ER + BC, next-generation SERDs demonstrated clinical activity, and elacestrant received an approval for advanced ESR1 -mutant disease. However, responses to these drugs were highly heterogeneous: across trials and independent of ESR1 status, 30–50% of patients progressed by their first follow-up scan while other patients sustained benefit for 2 years or more. Here, we interrogate the basis for heterogeneous responses by comparing biopsies from non-responding patients (NR; progression-free survival

Fields of Study & Subjects

Estrogen and related hormone effects Advanced Breast Cancer Therapies FOXO transcription factor regulation

Publication details

Journal / source
Nature Communications
Publisher
Springer Science and Business Media LLC
Volume
17
Issue
1
Publication date
1 April 2026
Language
EN