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Br J Cancer. 2014 Apr 2;110(7):1688-97. doi: 10.1038/bjc.2014.120. Epub 2014 Mar 11.

Nottingham Prognostic Index Plus (NPI+): a modern clinical decision making tool in breast cancer.

Author information

1
1] Breast Cancer Pathology Research Group, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK [2] Cellular Pathology, The Breast Institute, Nottingham University Hospitals NHS Trust, Nottingham, UK.
2
1] School of Computer Science, University of Nottingham, Nottingham, UK [2] Advanced Data Analysis Centre, University of Nottingham, Nottingham, UK.
3
Breast Cancer Pathology Research Group, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
4
College of Arts and Science, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
5
Cellular Pathology, The Breast Institute, Nottingham University Hospitals NHS Trust, Nottingham, UK.
6
School of Computer Science, University of Nottingham, Nottingham, UK.

Abstract

BACKGROUND:

Current management of breast cancer (BC) relies on risk stratification based on well-defined clinicopathologic factors. Global gene expression profiling studies have demonstrated that BC comprises distinct molecular classes with clinical relevance. In this study, we hypothesised that molecular features of BC are a key driver of tumour behaviour and when coupled with a novel and bespoke application of established clinicopathologic prognostic variables can predict both clinical outcome and relevant therapeutic options more accurately than existing methods.

METHODS:

In the current study, a comprehensive panel of biomarkers with relevance to BC was applied to a large and well-characterised series of BC, using immunohistochemistry and different multivariate clustering techniques, to identify the key molecular classes. Subsequently, each class was further stratified using a set of well-defined prognostic clinicopathologic variables. These variables were combined in formulae to prognostically stratify different molecular classes, collectively known as the Nottingham Prognostic Index Plus (NPI+). The NPI+ was then used to predict outcome in the different molecular classes.

RESULTS:

Seven core molecular classes were identified using a selective panel of 10 biomarkers. Incorporation of clinicopathologic variables in a second-stage analysis resulted in identification of distinct prognostic groups within each molecular class (NPI+). Outcome analysis showed that using the bespoke NPI formulae for each biological BC class provides improved patient outcome stratification superior to the traditional NPI.

CONCLUSION:

This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

PMID:
24619074
PMCID:
PMC3974073
DOI:
10.1038/bjc.2014.120
[Indexed for MEDLINE]
Free PMC Article

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