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01-12-2019 | Breast Cancer | Preclinical study

CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy

Authors: Lutfi H. Alfarsi, Rokaya El Ansari, Madeleine L. Craze, Michael S. Toss, Brendah Masisi, Ian O. Ellis, Emad A. Rakha, Andrew R. Green

Published in: Breast Cancer Research and Treatment | Issue 3/2019

Abstract

Purpose

Endocrine therapy is the standard treatment for oestrogen receptor positive (ER+) breast cancer. Despite its efficacy, around half of patients will develop resistance to this treatment and eventually relapse. Identification of effective and reliable biomarkers to predict the efficacy of endocrine therapy is of crucial importance in the management of ER+ breast cancer. Emerging evidence has revealed that the cell division regulator CDC20 exhibits an oncogenic function and plays important roles in tumourigenesis and progression of solid tumours. In this study, we investigated the prognostic and predictive role of CDC20 in early ER+ breast cancer patients.

Methods

The biological and clinical impact of CDC20 expression was assessed in large clinical annotated cohort of ER+ breast cancer with long-term follow-up at the mRNA level, using METABRIC and KM-Plotter datasets, and the protein level using immunohistochemistry on patients presenting at Nottingham. CDC20 expression was correlated with clinico-pathological parameters, molecular subtypes, clinical outcome and efficacy of endocrine therapy.

Results

High CDC20 mRNA expression was associated with poor clinico-pathological parameters including large tumour size and high tumour grade (P < 0.0001) in patients with ER+ breast cancer. High CDC20 mRNA expression was significantly associated with poor patient outcome (P < 0.0001). Importantly, high CDC20 expression was correlated with poor response to endocrine treatment in patients who treated with hormonal therapy only (P < 0.01). In multivariate analysis, CDC20 mRNA was an independent predictor of poor clinical outcome after treatment with endocrine therapy (P = 0.02).

Conclusion

CDC20 is a candidate biomarker for a subgroup of ER+ breast cancer characterised by poor clinical outcome. This study shows that the CDC20 could act as potential predictive biomarker of poor response to endocrine therapy in ER+ breast cancer.

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Title: CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy
Authors: Lutfi H. Alfarsi
Rokaya El Ansari
Madeleine L. Craze
Michael S. Toss
Brendah Masisi
Ian O. Ellis
Emad A. Rakha
Andrew R. Green
Publication date: 01-12-2019
Publisher: Springer US
Keywords: Breast Cancer
Breast Cancer
Biomarkers
Estrogens
Published in: Breast Cancer Research and Treatment / Issue 3/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-019-05420-8

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