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

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posted on 22.11.2019 by Paul B. Mullan, Victoria Bingham, Paula Haddock, Gareth W. Irwin, Elaine W. Kay, Stephen McQuaid, Niamh E. Buckley

BACKGROUND: 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 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.

METHODS: NUP98 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.

RESULTS: We 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.

CONCLUSIONS: We 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.

Funding

Breast Cancer Now (2012MaySF122). HSC Research and Development Division of the Public Health Agency in Northern Ireland and Cancer Research UK through the Belfast CRUK Centre and the Northern Ireland Experimental Cancer Medicine Centre. Friends of the Cancer Centre. The Northern Ireland Molecular Pathology Laboratory. Cancer Research UK, the Friends of the Cancer Centre. Sean Crummey Foundation.

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The original article is available at www.biomedcentral.com

Published Citation

Mullan PB, Bingham V, Haddock P, Irwin GW, Kay E, McQuaid S, Buckley NE. NUP98 - a novel predictor of response to anthracycline-based chemotherapy in triple negative breast cancer. BMC Cancer. 2019;19(1):236.

Publication Date

02/04/2019

Publisher

BioMed Central

PubMed ID

30935371

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