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Breast Cancer Res Treat. 2019 Jan;173(1):93-102. doi: 10.1007/s10549-018-4978-5. Epub 2018 Oct 10.

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

Author information

1
Nottingham Breast Cancer Research Centre, Division of Cancer and Stem Cells, School of Medicine, Nottingham City Hospital, University of Nottingham, 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, Nottingham City Hospital, University of Nottingham, Hucknall Road, Nottingham, NG5 1PB, UK. andrew.green@nottingham.ac.uk.

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.

KEYWORDS:

Breast cancer; Endocrine treatment; KIF18A; Oestrogen receptor; Predictive biomarker

PMID:
30306428
DOI:
10.1007/s10549-018-4978-5
[Indexed for MEDLINE]

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