Nottingham Prognostic Index Plus: validation of a clinical decision making tool in breast cancer in an independent series

Green, Andrew R.; Soria, Daniele; Stephen, Jacquelin; Powe, Desmond G.; Nolan, Christopher C.; Kunkler, Ian; Thomas, Jeremy; Kerr, Gillian R.; Jack, Wilma; Cameron, David; Piper, Tammy; Ball, Graham R.; Garibaldi, Jonathan M.; Rakha, Emad; Bartlett, John M.S.; Ellis, Ian O.

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), cyto-keratin (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.

Citation

Green, A. R., Soria, D., Stephen, J., Powe, D. G., Nolan, C. C., Kunkler, I., Thomas, J., Kerr, G. R., Jack, W., Cameron, D., Piper, T., Ball, G. R., Garibaldi, J. M., Rakha, E., Bartlett, J. M., & Ellis, I. O. (2016). Nottingham Prognostic Index Plus: validation of a clinical decision making tool in breast cancer in an independent series. Journal of Pathology: Clinical Research, 2, https://doi.org/10.1002/cjp2.32

• Journal Article Type: Article
• Acceptance Date: Oct 22, 2015
• Online Publication Date: Oct 27, 2015
• Publication Date: Jan 2, 2016
• Deposit Date: Jun 22, 2016
• Publicly Available Date: Jun 22, 2016
• Journal: Journal of Pathology: Clinical Research
• Electronic ISSN: 2056-4538
• Publisher: Wiley Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 2
• DOI: https://doi.org/10.1002/cjp2.32
• Keywords: Breast cancer; classification; prognostic index; molecular; clinical; outcom
• Public URL: https://nottingham-repository.worktribe.com/output/773953
• Publisher URL: http://onlinelibrary.wiley.com/doi/10.1002/cjp2.32/abstract;jsessionid=44BCA4E4E15E702668DC9439ADC03FC6.f04t02
• Contract Date: Jun 22, 2016