Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-01

AUTHORS

Lutfi H. Alfarsi, Rokaya Elansari, Michael S. Toss, Maria Diez-Rodriguez, Christopher C. Nolan, Ian O. Ellis, Emad A. Rakha, Andrew R. Green

ABSTRACT

PURPOSE: Identification of effective and reliable biomarkers that could be used to predict the efficacy of endocrine therapy is of crucial importance to the management of oestrogen receptor positive (ER+) breast cancer (BC). KIF18A, a key regulator of cell cycle, is overexpressed in many human cancers, including BC. In this study, we investigated the role of KIF18A as a biomarker to predict the benefit from endocrine treatment in early ER + BC patients. METHODS: KIF18A expression was assessed at the genomic level using the METABRIC dataset to explore its prognostic and predictive value in ER + BC patients (n = 1506). Predictive significance of KIF18A mRNA was validated using KM-Plot datasets (n = 2061). KIF18A protein expression was assessed using immunohistochemistry in a large annotated series of early-stage ER + BC (n = 1592) with long-term follow-up. RESULTS: High mRNA and protein expression of KIF18A were associated with short recurrence-free survival (RFS), distant-metastasis free survival (DMFS) and BC specific survival (all P < 0.05) in ER + BC in patients who received no adjuvant treatment or adjuvant endocrine therapy. In multivariate analysis, high KIF18A expression was an independent prognostic biomarker for poor RFS (P = 0.027) and DMFS (P = 0.028) in patients treated with adjuvant endocrine therapy. CONCLUSION: KIF18A appears to be a candidate biomarker of a subgroup of ER + BC characterised by poor clinical outcome. High KIF18A expression has prognostic significance to predict poor benefit from endocrine treatment for patients with ER + BC. Therefore, measurement of KIF18A on ER + BC patients prior to treatment could guide clinician decision on benefit from endocrine therapy. More... »

PAGES

93-102

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-018-4978-5

DOI

http://dx.doi.org/10.1007/s10549-018-4978-5

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1107532730

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30306428


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