A combination of Nottingham prognostic index (NPI) and IHC4 score as a cost-effective tool in the risk stratification of breast cancer patients
Authors: Vijayakumar Madhulika , Sreeniva Vidhyalakshmi , Sekar Vimala 
Published: November 2022

Abstract
Background: Breast cancer has gained the limelight over the past few decades for being the most common cause of cancer associated morbidity and mortality of women worldwide. Breast cancer, in developing countries like India, has a major impact on both the social and economical grounds. The proportional prevalence of breast cancer is higher in younger age groups in countries like India than the global average, making it a great concern as it carries a poorer prognosis. Breast cancer, like many other neoplasms, is an umbrella term and represents a complex heterogenous group of tumors controlled by a multitude of genetic and epigenetic alterations, with varied phenotypic and genotypic features and also the response to therapy. The recent advances of improved diagnostic screening and the elucidation of molecular mechanisms responsible for the disease, resulting in the availability of better treatment modalities have contributed to the progress in the management of patients with breast cancers and their improved survival. Hence it becomes necessary to read the prognosis of breast cancer patients and their survival outcome. The Nottingham prognostic index (NPI) is clinically relevant, internationally validated and established prognostication tool for classifying breast tumors into three or more prognostic groups, which was established in the year 1982 by Galea et al. NPI score is calculated by combining the tumor size, histological grade and nodal status reflecting the growth rate, genetic instability and the metastatic behavior of the breast cancers.Immunohistochemical4 score (IHC4) is an inexpensive gene expression-profiling tool which incorporates immunohistochemical parameters ER, progesterone receptor (PgR), HER2 and Ki67. Here, we studied the combination of Nottingham prognostic index (NPI) and IHC4 score as a cost effective tool in the risk stratification of breast cancer patients.
Materials and Methods: This retrospective cohort study included 50 patients diagnosed with and undergoing treatment for breast cancers in the medical oncology department of PSG Institute of Medical Sciences and Research during the period of January 2016 to December 2018. The Nottingham prognostic index was calculated based on size of the tumour, histologic grade and lymph node status. The results of immunohistochemistry was obtained from the archives and IHC4 score was also calculated. The tumours were classified into Luminal A, Luminal B, Her 2 neu and basal like based on the results of immunohistochemistry. All patients were followed up for a period of 2 years.
Results: Out of 50 patients, 8 patients had good prognostic score according to Nottingham prognostic index (NPI < 3.4), 28 had intermediate and 14 had poor prognosis (> 5.4).14 patients belonged to luminal A, 15 of them to luminal B, 12 to HER 2 neu and 9 were triple negative. The NPI prognostic groups were compared with IHC4 score groups and also the molecular subtypes.
Conclusion: In this study, we observed that the patients belonging to same NPI group had different classes of IHC4 scores and were classifiable into different molecular subtypes. Also on follow up of these patients 5 of the patients developed metastatic disease or recurrence were either triple negative with a very high Ki67 proliferation rate or HER2 neu subtype. Nevertheless, tumours with Luminal A subtype but a very high NPI also recurred within a year. Hence , this retrospective cohort study showed that a combination of NPI and IHC4 score can be used as a costeffective alternative to other more expensive molecular tests in the risk stratification and to predict the prognosis.