Lutfi H Alfarsi1, Rokaya El Ansari1, Madeleine L Craze1, Michael S Toss1, Brendah Masisi1, Ian O Ellis1,2, Emad A Rakha1,2, Andrew R Green3. 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. 2. Cellular Pathology, Nottingham University Hospitals NHS Trust, Hucknall Road, Nottingham, NG5 1PB, UK. 3. 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. andrew.green@nottingham.ac.uk.
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.
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 cancerpatients. 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.
Entities:
Keywords:
Breast cancer; CDC20; ER; Endocrine resistance; Predictive biomarker
Authors: Lutfi H Alfarsi; Rokaya El Ansari; Madeleine L Craze; Brendah K Masisi; Ian O Ellis; Emad A Rakha; Andrew R Green Journal: BMC Cancer Date: 2020-05-14 Impact factor: 4.430
Authors: Lutfi H Alfarsi; Rokaya El Ansari; Brendah K Masisi; Ruth Parks; Omar J Mohammed; Ian O Ellis; Emad A Rakha; Andrew R Green Journal: Cancers (Basel) Date: 2020-06-12 Impact factor: 6.639