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Correlation analysis between molecular subtypes and Nottingham Prognostic Index in breast cancer.

ABSTRACT: Molecular subtypes and Nottingham Prognostic Index (NPI) are both prognostic models for breast cancer patients. We evaluated the association between molecular subtypes and NPI in 1042 breast cancer patients. The molecular subtypes indicating poorer prognosis were positively correlated to higher NPI (r = 0.138, P = 0.001). ER positive expression and PR high expression were positively correlated with NPI (r = 0.142, P = 0.001; r = 0.139, P = 0.001; respectively) and negatively correlated with histological grade (r = -0.233, P < 0.001; r = -0.176, P < 0.001; respectively). Ki67 status was negatively correlated with NPI and positively correlated with histological grade (r = -0.120, P =0.004; r = 0.197, P < 0.001; respectively). The percentages of cases with NPI score 2.00-3.40 were higher in the luminar A, ER+, PR high expression and Ki67 low expression group, and the percentages of cases with NPI > 5.40 were higher in the HER2 overexpression subtype, basal-like subtype, ER-, PR low/negative expression, and Ki67 high expression groups. The excellent consistence was observed between histological grade and molecular subtypes, ER, PR, Ki67. The difference of histological grade between the HER2 positive and negative group was statistically significant. In conclusion, there was closely association between molecular subtypes and NPI in breast cancer. For further comparing the prognostic significance of molecular subtypes and NPI, survival analyses should be performed on the same population in a large-scale prospective study.

SUBMITTER: Zhen H

PROVIDER: S-EPMC5650325 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Correlation analysis between molecular subtypes and Nottingham Prognostic Index in breast cancer.

Zhen Hongchao H Yang Liuting L Li Li L Yu Junxian J Zhao Lei L Li Yingying Y Li Qin Q

Oncotarget 20170527 43

Molecular subtypes and Nottingham Prognostic Index (NPI) are both prognostic models for breast cancer patients. We evaluated the association between molecular subtypes and NPI in 1042 breast cancer patients. The molecular subtypes indicating poorer prognosis were positively correlated to higher NPI (r = 0.138, P = 0.001). ER positive expression and PR high expression were positively correlated with NPI (r = 0.142, P = 0.001; r = 0.139, P = 0.001; respect ...[more]

PMID: 29088770

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Project description:BACKGROUND: A breast cancer prognostic tool should ideally be applicable to all types of invasive breast lesions. A number of studies have shown histopathological grade to be an independent prognostic factor in breast cancer, adding prognostic power to nodal stage and tumour size. The Nottingham Prognostic Index has been shown to accurately predict patient outcome in stratified groups with a follow-up period of 15 years after primary diagnosis of breast cancer. Clinically, breast tumours that lack the expression of Oestrogen Receptor, Progesterone Receptor and Human Epidermal growth factor Receptor 2 (HER2) are identified as presenting a "triple-negative" phenotype or as triple-negative breast cancers. These poor outcome tumours represent an easily recognisable prognostic group of breast cancer with aggressive behaviour that currently lack the benefit of available systemic therapy. There are conflicting results on the prevalence of lymph node metastasis at the time of diagnosis in triple-negative breast cancer patients but it is currently accepted that triple-negative breast cancer does not metastasize to axillary nodes and bones as frequently as the non-triple-negative carcinomas, favouring instead, a preferentially haematogenous spread. Hypothetically, this particular tumour dissemination pattern would impair the reliability of using Nottingham Prognostic Index as a tool for triple-negative breast cancer prognostication. METHODS: The present study tested the effectiveness of the Nottingham Prognostic Index in stratifying breast cancer patients of different subtypes with special emphasis in a triple-negative breast cancer patient subset versus non- triple-negative breast cancer. RESULTS: We demonstrated that besides the fact that TNBC disseminate to axillary lymph nodes as frequently as luminal or HER2 tumours, we also showed that TNBC are larger in size compared with other subtypes and almost all grade 3. Additionally, survival curves demonstrated that these prognostic factors are equally important to stratify different survival outcomes in non-TNBC as in TNBC. We also showed that the NPI retains the ability to stratify and predict survival of TNBC patients. CONCLUSION: The importance of this study relies on the need of prognostication improvements on TNBC, showing, at a clinical standpoint, that Nottingham Prognostic Index is as a truthful prognostic tool in TNBC.

Project description: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.

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Correlation analysis between molecular subtypes and Nottingham Prognostic Index in breast cancer.

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Correlation analysis between molecular subtypes and Nottingham Prognostic Index in breast cancer.

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