Language

English

Publication Date

4-2-2025

Journal

Cancer Discovery

DOI

10.1158/2159-8290.CD-23-0543

PMID

39835789

PMCID

PMC11964846

PubMedCentral® Posted Date

10-2-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Bone metastases can disseminate to secondary sites and promote breast cancer progression creating additional clinical challenges. The mechanisms contributing to secondary metastasis are barely understood. Here, we evaluate the prediction power of Her2-expressing (Her2E) circulating tumor cells (CTCs) after analyzing over 13,000 CTCs from a cohort of 137 metastatic breast cancer (MBC) patients with initial HR+/Her2− status and employ preclinical models of bone metastasis (BM) to validate the role of Her2E CTCs in multi-organ metastases. While Her2 expression was higher in patients with bone metastasis, experimental analyses revealed that Her2E CTCs derived from bone lesions were more dependent on Her2 activity and more susceptible to anti-Her2 therapy. Targeting the bone-mediated Her2 induction reduces CTC detection and abrogates secondary metastasis from bone. Overall, we elucidate that Her2E CTCs can serve as a non-invasive biomarker for BM formation with high therapeutic benefit for HR+ MBC patients.

Keywords

Humans, Breast Neoplasms, Female, Receptor, ErbB-2, Bone Neoplasms, Animals, Mice, Cell Line, Tumor, Neoplasm Metastasis, Biomarkers, Tumor

Published Open-Access

yes

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