The Signal Transducer IL6ST (gp130) as a Predictive and Prognostic Biomarker in Breast Cancer.

Carlos Martínez-Pérez,Arran K Turnbull,J Michael Dixon,Mark Gray,Jess Leung,James Meehan,Charlene Kay

doi:10.3390/jpm11070618

Abstract

Novel biomarkers are needed to continue to improve breast cancer clinical management and outcome. IL6-like cytokines, whose pleiotropic functions include roles in many hallmarks of malignancy, rely on the signal transducer IL6ST (gp130) for all their signalling. To date, 10 separate independent studies based on the analysis of clinical breast cancer samples have identified IL6ST as a predictor. Consistent findings suggest that IL6ST is a positive prognostic factor and is associated with ER status. Interestingly, these studies include 4 multigene signatures (EndoPredict, EER4, IRSN-23 and 42GC) that incorporate IL6ST to predict risk of recurrence or outcome from endocrine or chemotherapy. Here we review the existing evidence on the promising predictive and prognostic value of IL6ST. We also discuss how this potential could be further translated into clinical practice beyond the EndoPredict tool, which is already available in the clinic. The most promising route to further exploit IL6ST’s promising predicting power will likely be through additional hybrid multifactor signatures that allow for more robust stratification of ER+ breast tumours into discrete groups with distinct outcomes, thus enabling greater refinement of the treatment-selection process.

Highlights

The Essential Role of Biomarkers in Breast CancerBreast cancer (BC) is a heterogeneous disease comprising well-characterised molecular subtypes that differ in their oncogenic drivers, pathogenesis and prognosis
In 2011, Filipits et al presented a prognostic signature named EndoPredict (EP) that predicted the likelihood of distant recurrence (DR) at 5 and 10-years in patients with ER+/human epidermal growth factor receptor 2 (HER2)- Breast CancerBreast cancer (BC) treated with endocrine therapy (ET) alone [44]
interleukin-6 signal transducer (IL6ST) has emerged as a biomarker with prognostic and predictive value in BC

Summary

Background

Breast cancer (BC) is a heterogeneous disease comprising well-characterised molecular subtypes that differ in their oncogenic drivers, pathogenesis and prognosis. A biomarker might be utilised qualitatively or quantitatively, as a continuous variable or with discrete cut-offs, alone or in combination with other markers in the form of multifactor tests or signatures In their different capacities, biomarkers are highly valuable in disease detection, staging, monitoring or prognosis estimation and they can guide the treatment selection and decision-making process in the management of many cancers, including breast [3]. Evidence suggests that the current diagnostic tools and available biomarkers fail to sufficiently discriminate the underlying heterogeneity of the disease Both basic and translational research continue to add to our understanding of the complex and evolving biology, shedding light on the pathways and mechanisms involved in phenomena such as the development of acquired resistance to treatment. We will review the evidence on one molecule in particular, the interleukin-6 signal transducer (IL6ST), which has emerged as a novel and exciting BC biomarker in recent years

The IL6-Like Cytokine Family and Its Signalling in Breast Cancer

IL6ST as an Independent Predictor in BC

EndoPredict and EPclin Scores for Prediction of Risk of Distant Recurrence

Findings

Discussion

Conclusions