title: Nottingham Prognostic Index Plus: Validation of a clinical decision making tool in breast cancer in an independent series.
abstract: The Nottingham Prognostic Index Plus (NPI+) is a clinical decision making tool in breast cancer (BC) that aims to provide improved patient outcome stratification superior to the traditional NPI. This study aimed to validate the NPI+ in an independent series of BC. Eight hundred and eighty five primary early stage BC cases from Edinburgh were semi-quantitatively assessed for 10 biomarkers [Estrogen Receptor (ER), Progesterone Receptor (PgR), cytokeratin (CK) 5/6, CK7/8, epidermal growth factor receptor (EGFR), HER2, HER3, HER4, p53, and Mucin 1] using immunohistochemistry and classified into biological classes by fuzzy logic-derived algorithms previously developed in the Nottingham series. Subsequently, NPI+ Prognostic Groups (PGs) were assigned for each class using bespoke NPI-like formulae, previously developed in each NPI+ biological class of the Nottingham series, utilising clinicopathological parameters: number of positive nodes, pathological tumour size, stage, tubule formation, nuclear pleomorphism and mitotic counts. Biological classes and PGs were compared between the Edinburgh and Nottingham series using Cramer's V and their role in patient outcome prediction using Kaplan-Meier curves and tested using Log Rank. The NPI+ biomarker panel classified the Edinburgh series into seven biological classes similar to the Nottingham series (p > 0.01). The biological classes were significantly associated with patient outcome (p < 0.001). PGs were comparable in predicting patient outcome between series in Luminal A, Basal p53 altered, HER2+/ER+ tumours (p > 0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER2+/ER- tumours and the poor PG in the Luminal N class (p > 0.01). Due to small patient numbers assigned to the remaining PGs, Luminal N, Luminal B, Basal p53 normal and HER2+/ER- classes could not be validated. This study demonstrates the reproducibility of NPI+ and confirmed its prognostic value in an independent cohort of primary BC. Further validation in large randomised controlled trial material is warranted.
authors: Division of Cancer and Stem Cells Breast Cancer Pathology Research Group, School of Medicine, University of Nottingham, Nottingham City Hospital Hucknall Road Nottingham NG5 1PB.
authors: Andrew R
authors: AR
authors: Green
authors: Intelligent Modelling & Analysis Research GroupSchool of Computer ScienceUniversity of Nottingham, Jubilee CampusWollaton RoadNottinghamNG8 1BB; Advanced Data Analysis Centre, University of Nottingham, University ParkNottinghamNG7 2RD.
authors: Daniele
authors: D
authors: Soria
authors: School of Molecular, Genetic and Population Health Sciences Centre for Population Health Sciences, Medical School, University of Edinburgh Teviot Place Edinburgh EH8 9AG.
authors: Jacqueline
authors: J
authors: Stephen
authors: Cellular Pathology, Nottingham University Hospitals NHS Trust Hucknall Road Nottingham NG5 1PB.
authors: Desmond G
authors: DG
authors: Powe
authors: Division of Cancer and Stem Cells Breast Cancer Pathology Research Group, School of Medicine, University of Nottingham, Nottingham City Hospital Hucknall Road Nottingham NG5 1PB.
authors: Christopher C
authors: CC
authors: Nolan
authors: The Institute of Genetics and Molecular Medicine Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital Crewe Road South Edinburgh EH4 2XR.
authors: Ian
authors: I
authors: Kunkler
authors: Edinburgh Breast Unit, Western General Hospital Crewe Road South Edinburgh EH4 2XU.
authors: Jeremy
authors: J
authors: Thomas
authors: The Institute of Genetics and Molecular Medicine Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital Crewe Road South Edinburgh EH4 2XR.
authors: Gillian R
authors: GR
authors: Kerr
authors: Edinburgh Breast Unit, Western General Hospital Crewe Road South Edinburgh EH4 2XU.
authors: Wilma
authors: W
authors: Jack
authors: The Institute of Genetics and Molecular Medicine Edinburgh Cancer Research Centre, University of Edinburgh, Western General Hospital Crewe Road South Edinburgh EH4 2XR.
authors: David
authors: D
authors: Cameron
authors: Edinburgh Breast Unit, Western General Hospital Crewe Road South Edinburgh EH4 2XU.
authors: Tammy
authors: T
authors: Piper
authors: John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University Nottingham NG11 8NS.
authors: Graham R
authors: GR
authors: Ball
authors: Intelligent Modelling & Analysis Research GroupSchool of Computer ScienceUniversity of Nottingham, Jubilee CampusWollaton RoadNottinghamNG8 1BB; Advanced Data Analysis Centre, University of Nottingham, University ParkNottinghamNG7 2RD.
authors: Jonathan M
authors: JM
authors: Garibaldi
authors: Division of Cancer and Stem CellsBreast Cancer Pathology Research Group, School of Medicine, University of Nottingham, Nottingham City HospitalHucknall RoadNottinghamNG5 1PB; Cellular Pathology, Nottingham University Hospitals NHS TrustHucknall RoadNottinghamNG5 1PB.
authors: Emad A
authors: EA
authors: Rakha
authors: The Institute of Genetics and Molecular MedicineEdinburgh Cancer Research Centre, University of Edinburgh, Western General HospitalCrewe Road SouthEdinburghEH4 2XR; Transformative PathologyOntario Institute for Cancer Research, MaRS Centre661 University Avenue, Suite 510TorontoCanadaM5G 0A3.
authors: John Ms
authors: JM
authors: Bartlett
authors: Division of Cancer and Stem CellsBreast Cancer Pathology Research Group, School of Medicine, University of Nottingham, Nottingham City HospitalHucknall RoadNottinghamNG5 1PB; Cellular Pathology, Nottingham University Hospitals NHS TrustHucknall RoadNottinghamNG5 1PB.
authors: Ian O
authors: IO
authors: Ellis
keywords: breast cancer; classification; clinical; molecular; outcome; prognostic index