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

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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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Acknowledgements

We thank the Nottingham Health Science Biobank and Breast Cancer Now Tissue Bank for the provision of tissue samples. We thank the Saudi Arabia Cultural Embassy for funding.

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Authors and Affiliations

  1. Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK

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

  2. Cellular Pathology, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, NG5 1PB, UK

    Ian O. Ellis & Emad A. Rakha

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  1. Lutfi H. Alfarsi
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  2. Rokaya El Ansari
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  3. Madeleine L. Craze
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  5. Brendah Masisi
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Correspondence to Andrew R. Green.

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The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

Ethical approval

This study was performed according to the REMARK guidelines for tumour prognostic studies [39], and approved by the Nottingham Research Ethics Committee 2 under the title “Development of a molecular genetic classification of breast cancer”.

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Informed consent was obtained from the participants included in the study.

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Alfarsi, L.H., Ansari, R.E., Craze, M.L. et al. CDC20 expression in oestrogen receptor positive breast cancer predicts poor prognosis and lack of response to endocrine therapy. Breast Cancer Res Treat 178, 535–544 (2019). https://doi.org/10.1007/s10549-019-05420-8

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