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Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer

Green, Andrew R.; Soria, Daniele; Powe, Desmond G.; Nolan, Christopher C.; Aleskandarany, Mohammed A.; Sz�sz, M.A.; T?k�s, A.M.; Ball, G.R.; Garibaldi, Jonathan M.; Rakha, Emad; Kulka, J.; Ellis, Ian O.

Nottingham prognostic index plus (NPI+) predicts risk of distant metastases in primary breast cancer Thumbnail


Daniele Soria

Desmond G. Powe

Christopher C. Nolan

Mohammed A. Aleskandarany

M.A. Sz�sz

A.M. T?k�s

G.R. Ball

Jonathan M. Garibaldi

Professor of Breast Cancer Pathology

J. Kulka

Ian O. Ellis


The Nottingham prognostic index plus (NPI+) is based on the assessment of biological class combined with established clinicopathologic prognostic variables providing improved patient outcome stratification for breast cancer superior to the traditional NPI. This study aimed to determine prognostic capability of the NPI+ in predicting risk of development of distant disease. A well-characterised series of 1073 primary early-stage BC cases treated in Nottingham and 251 cases from Budapest were immunohistochemically assessed for cytokeratin (Ck)5/6, Ck18, EGFR, oestrogen receptor (ER), progesterone receptor, HER2, HER3, HER4, Mucin 1 and p53 expression. NPI+ biological class and prognostic scores were assigned using individual algorithms for each biological class incorporating clinicopathologic parameters and investigated in terms of prediction of distant metastases-free survival (MFS). The NPI+ identified distinct prognostic groups (PG) within each molecular class which were predictive of MFS providing improved patient outcome stratification superior to the traditional NPI. NPI+ PGs, between series, were comparable in predicting patient outcome between series in luminal A, basal p53 altered and HER2+/ER+ (p > 0.01) tumours. The low-risk groups were similarly validated in luminal B, luminal N, basal p53 normal tumours (p > 0.01). Due to small patient numbers the remaining PGs could not be validated. NPI+ was additionally able to predict a higher risk of metastases at certain distant sites. This study may indicate the NPI+ as a useful tool in predicting the risk of metastases. The NPI+ provides accurate risk stratification allowing improved individualised clinical decision making for breast cancer.

Journal Article Type Article
Acceptance Date Apr 19, 2016
Online Publication Date Apr 26, 2016
Publication Date May 1, 2016
Deposit Date May 21, 2016
Publicly Available Date May 21, 2016
Journal Breast Cancer Research and Treatment
Print ISSN 0167-6806
Electronic ISSN 0167-6806
Publisher Springer Verlag
Peer Reviewed Peer Reviewed
Volume 157
Issue 1
Pages 65-75
Keywords Breast cancer; classification; prognostic index; molecular; clinical; outcome
Public URL
Publisher URL
Additional Information Erratum: Unfortunately, the original article was published under CC
BY-NC license, which is not compliant with the author
funder’s OA policy. The article’s correct licence is CC BY
license and the correct open access statement is given
Open access: This article is distributed under the terms
of the Creative Commons Attribution 4.0 International
License (, which
permits unrestricted use, distribution, and reproduction in
any medium, provided you give appropriate credit to the
original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were


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