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

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

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? less than 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.

Citation

Alfarsi, L. H., Elansari, R., Toss, M. S., Diez-Rodriguez, M., Nolan, C. C., Ellis, I. O., …Green, A. R. (2018). Kinesin family member-18A (KIF18A) is a predictive biomarker of poor benefit from endocrine therapy in early ER+ breast cancer. Breast Cancer Research and Treatment, https://doi.org/10.1007/s10549-018-4978-5

• Journal Article Type: Article
• Acceptance Date: Sep 29, 2018
• Online Publication Date: Oct 10, 2018
• Publication Date: Oct 10, 2018
• Deposit Date: Oct 12, 2018
• Publicly Available Date: Oct 11, 2019
• Journal: Breast Cancer Research and Treatment
• Print ISSN: 0167-6806
• Electronic ISSN: 1573-7217
• Publisher: BMC
• Peer Reviewed: Peer Reviewed
• DOI: https://doi.org/10.1007/s10549-018-4978-5
• Keywords: Cancer Research; Oncology
• Public URL: https://nottingham-repository.worktribe.com/output/1162675
• Publisher URL: https://link.springer.com/article/10.1007%2Fs10549-018-4978-5