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Breast Cancer Research
Published in: Breast Cancer Research 1/2020

01-12-2020 | Breast Cancer | Research article

A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer

Authors: Lori J. Goldstein, Raymond P. Perez, Denise Yardley, Linda K. Han, James M. Reuben, Hui Gao, Susan McCanna, Beth Butler, Pier Adelchi Ruffini, Yi Liu, Roberto R. Rosato, Jenny C. Chang

Published in: Breast Cancer Research | Issue 1/2020

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Abstract

Background

Cancer stem cells (CSCs) are purported to be responsible for tumor initiation, treatment resistance, disease recurrence, and metastasis. CXCR1, one of the receptors for CXCL8, was identified on breast cancer (BC) CSCs. Reparixin, an investigational allosteric inhibitor of CXCR1, reduced the CSC content of human BC xenograft in mice.

Methods

In this multicenter, single-arm trial, women with HER-2-negative operable BC received reparixin oral tablets 1000 mg three times daily for 21 days before surgery. Primary objectives evaluated the safety of reparixin and the effects of reparixin on CSC and tumor microenvironment in core biopsies taken at baseline and at treatment completion. Signal of activity was defined as a reduction of ≥ 20% in ALDH+ or CD24−/CD44+ CSC by flow cytometry, with consistent reduction by immunohistochemistry.

Results

Twenty patients were enrolled and completed the study. There were no serious adverse reactions. CSC markers ALDH+ and CD24−/CD44+ measured by flow cytometry decreased by ≥ 20% in 4/17 and 9/17 evaluable patients, respectively. However, these results could not be confirmed by immunofluorescence due to the very low number of CSC.

Conclusions

Reparixin appeared safe and well-tolerated. CSCs were reduced in several patients as measured by flow cytometry, suggesting targeting of CXCR1 on CSC.

Clinical trial registration

Clinicaltrials.gov, NCT01861054. Registered on April 18, 2013.
Appendix
Available only for authorised users
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Metadata
Title
A window-of-opportunity trial of the CXCR1/2 inhibitor reparixin in operable HER-2-negative breast cancer
Authors
Lori J. Goldstein
Raymond P. Perez
Denise Yardley
Linda K. Han
James M. Reuben
Hui Gao
Susan McCanna
Beth Butler
Pier Adelchi Ruffini
Yi Liu
Roberto R. Rosato
Jenny C. Chang
Publication date
01-12-2020
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-019-1243-8

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