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Endothelin-1 Enriched Tumor Phenotype Predicts Breast Cancer Recurrence

Authors :
Alla Sikorskii
Cheryl Leece
Shalini Chitneni
Burra V. Madhukar
Kathleen A. Gallo
Nikolay V. Dimitrov
David Wiese
Deimante Tamkus
Simona C. Chivu
Source :
ISRN Oncology
Publication Year :
2013
Publisher :
Hindawi Limited, 2013.

Abstract

Introduction. Breast cancer recurrence can develop years after primary treatment. Crosstalk between breast cancer cells and their stromal microenvironment may influence tumor progression. Our primary study aim was to determine whether endothelin-1 (ET-1) expression in tumor and stroma predicts breast cancer relapse. The secondary aim was to determine ET-1/endothelin receptor A (ETAR) role on signaling pathways and apoptosis in breast cancer. Experimental Design. Patients with histologically documented stages I–III invasive breast cancer were included in the study. ET-1 expression by immunohistochemistry (IHC) in tumor cells and stroma was analyzed. Association between ET-1 expression and clinical outcome was assessed using multivariate Cox proportional hazard model. Kaplan-Meier curves were used to estimate disease-free survival (DFS). In addition, the effect of ET-1/ETAR on signaling pathways and apoptosis was evaluated in MCF-7 and MDA-MB-231 breast cancer cells. Results. With a median followup of 7 years, ET-1 non-enriched tumor phenotype had a significant association with favorable disease-free survival (HR=0.16; 95% CI 0.03–0.77; P value Conclusions. We found ET-1 expression in tumor and stroma to be an independent prognostic marker for breast cancer recurrence. Prospective studies are warranted to examine whether ET-1 expression in tumor/stroma could assist in stratifying patients with hormone receptor positive breast cancer for adjuvant therapy.

Details

ISSN :
2090567X
Volume :
2013
Database :
OpenAIRE
Journal :
ISRN Oncology
Accession number :
edsair.doi.dedup.....3ef7760c6d35590d19c9da7f4a6726ce