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

Rakha, Emad; Soria, Daniele; Green, Andrew R.; Lemetre, Christophe; Powe, Desmond G.; Nolan, Christopher C.; Garibaldi, Jonathan M.; Ball, Graham; Ellis, Ian O.

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Professor of Breast Cancer Pathology

Daniele Soria

Andrew R. Green

Christophe Lemetre

Desmond G. Powe

Christopher C. Nolan

Jonathan M. Garibaldi

Graham Ball

Ian O. Ellis


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 hypothesized 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. 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+). NPI+ was then used to predict outcome in the different molecular classes with.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 breast cancer class provides improved patient outcome stratification superior to the traditional NPI. This study provides proof-of-principle evidence for the use of NPI+ in supporting improved individualised clinical decision making.

Journal Article Type Article
Publication Date Mar 11, 2014
Deposit Date Jan 30, 2015
Publicly Available Date Jan 30, 2015
Journal British Journal of Cancer
Print ISSN 0007-0920
Electronic ISSN 0007-0920
Publisher Cancer Research UK
Peer Reviewed Peer Reviewed
Volume 110
Issue 7
Public URL
Publisher URL