NUP98 \u2013 a novel predictor of response to anthracycline-based chemotherapy in triple negative breast cancer

Paul B Mullan,Elaine Kay,Victoria Bingham,Stephen Mcquaid,Gareth W Irwin,Paula Haddock,Niamh E Buckley

doi:10.1186/s12885-019-5407-9

Abstract

BackgroundTriple Negative breast cancer (TNBC) is a poor outcome subgroup of breast cancer defined based on the absence of expression of ERα and PR and HER2 amplification. These hard to treat cancers lack targeted treatment options and are therefore treated with a standard of care (SoC) generic cocktail of DNA damaging chemotherapy, with a wide range of clinical responses. While a subset of TNBC patients respond very well to this treatment, others receive no clinical benefit and die from their disease within a short time period. We currently lack biomarkers to prospectively identify patients likely to relapse and we lack alternate treatment options.MethodsNUP98 protein expression was investigated in patient samples using two independent tissue microarrays (TMAs), as well as a normal breast TMA. Correlation with pathological response to various chemotherapy regimens was investigated.ResultsWe have shown that high NUP98 is significantly associated with poor outcome in TNBC patient samples both by gene expression and IHC-based protein analysis. While trends linking NUP98 expression with poorer outcomes were observed in breast cancer overall (and more specifically in the LuminalB Her2- subgroup), significant correlations were observed in TNBC. This appeared to be specific to anthracycline based regimens as the association between NUP98 and response was not observed in patients treated with taxane-based chemotherapy.ConclusionsWe have identified a novel biomarker, NUP98, that can predict response to anthracycline based chemotherapy in TNBC. The ability to prospectively identify patients who are less likely to respond to SoC chemotherapy is a vital step in improving the overall survival of these patients.

Highlights

Triple Negative breast cancer (TNBC) is a poor outcome subgroup of breast cancer defined based on the absence of expression of Estrogen receptor alpha (ERα) and Progesterone Receptor (PR) and HER2 amplification
We currently lack biomarkers to prospectively identify which patients are likely to respond to standard of care (SoC) and which are not and should have an alternate treatment plan
We identified and validated the nuclear pore protein, NUP98, as a novel biomarker associated with poor outcome in TNBC in the context of SoC anthracycline based treatment

Summary

Introduction

Triple Negative breast cancer (TNBC) is a poor outcome subgroup of breast cancer defined based on the absence of expression of ERα and PR and HER2 amplification These hard to treat cancers lack targeted treatment options and are treated with a standard of care (SoC) generic cocktail of DNA damaging chemotherapy, with a wide range of clinical responses. The second group, displaying residual disease (RD) following treatment, have much poorer outcome compared to non-TNBC with only 68% of patients alive 3 years post-treatment compared to 88% [2]. This demonstrates that overall survival in TNBC is intrinsically linked to the response to first line chemotherapy. We currently lack biomarkers to prospectively identify which patients are likely to respond to SoC and which are not and should have an alternate treatment plan

Methods

Results

Conclusion