Nottingham prognostic index plus: Validation of a clinical decision making tool in breast cancer in an independent series

Abstract

The Nottingham Prognostic Index Plus (NPI1) 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 NPI1 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, NPI1 Prognostic Groups (PGs) were assigned for each class using bespoke NPI-like formulae, previously developed in each NPI1 biological class of the Nottingham series, utilizing 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 NPI1 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, HER21/ER1 tumours (p >0.01). The good PGs were similarly validated in Luminal B, Basal p53 normal, HER21/ ER2 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 HER21/ER2 classes could not be validated. This study demonstrates the reproducibility of NPI1 and confirmed its prognostic value in an independent cohort of primary BC. Further validation in large randomised controlled trial material is warranted.