Abstract
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. 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. 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). 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.
Highlights
Breast cancer is a heterogeneous disease with various biological subtypes [1] with the most common form, approximately 75%, of breast cancer being oestrogen receptor posi\ve (ER+) [2,3]
Cell division cycle 20 homolog (CDC20) expression in ER+ BC High CDC20 mRNA expression in the METABRIC cohort was observed in 870 cases (58%), where low expression was observed in 636 cases (42%)
We focused on the role of CDC20 in ER+ breast cancer and especially in pa\ents who were treated with only endocrine therapy
Summary
Breast cancer is a heterogeneous disease with various biological subtypes [1] with the most common form, approximately 75%, of breast cancer being oestrogen receptor posi\ve (ER+) [2,3]. Endocrine therapy is the main treatment for ER+ tumours, which has vastly improved survival and has reduced mortality [4]. A high propor\on of pa\ents receiving adjuvant endocrine therapy s\ll experience relapse and become resistant to treatment [5,6]. Its overexpression is suggested as a biomarker of poor outcome in pancrea\c [14], colon [15], primary non-small cell lung [16] and ovarian cancer [11]. In terms of breast cancer, two reports have demonstrated that CDC20 is a poten\al key player in the progression of breast cancer where it is significantly higher in breast cancer cells and high-grade primary tumour \ssues [17] and indicates an aggressive course of disease risk [18]. In par\cular, we assessed whether CDC20 had a role in endocrine resistance which could be used to improve therapy predic\on in ER+ breast cancer
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