Nottingham prognostic x (NPx): a risk stratification tool in ER-positive HER2-negative breast cancer: a validation study

Histopathology. 2024 Sep;85(3):468-477. doi: 10.1111/his.15234. Epub 2024 Jun 13.

Abstract

Aims: In this study, we validate the use of Nottingham Prognostic x (NPx), consisting of tumour size, tumour grade, progesterone receptor (PR) and Ki67 in luminal BC.

Materials and methods: Two large cohorts of luminal early-stage BC (n = 2864) were included. PR and Ki67 expression were assessed using full-face resection samples using immunohistochemistry. NPx was calculated and correlated with clinical variables and outcome, together with Oncotype DX recurrence score (RS), that is frequently used as a risk stratifier in luminal BC.

Results: In the whole cohort, 38% of patients were classified as high risk using NPx which showed significant association with parameters characteristics of aggressive tumour behaviour and shorter survival (P < 0.0001). NPx classified the moderate Nottingham Prognostic Index (NPI) risk group (n = 1812) into two distinct prognostic subgroups. Of the 82% low-risk group, only 3.8% developed events. Contrasting this, 14% of the high-risk patients developed events during follow-up. A strong association was observed between NPx and Oncotype Dx RS (P < 0.0001), where 66% of patients with intermediate risk RS who had subsequent distant metastases also had a high-risk NPx.

Conclusion: NPx is a reliable prognostic index in patients with luminal early-stage BC, and in selected patients may be used to guide adjuvant chemotherapy recommendations.

Keywords: Ki67; Nottingham PX; PR; breast cancer; endocrine therapy; risk.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor* / analysis
  • Biomarkers, Tumor* / metabolism
  • Breast Neoplasms* / diagnosis
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / mortality
  • Breast Neoplasms* / pathology
  • Female
  • Humans
  • Ki-67 Antigen / analysis
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Prognosis
  • Receptor, ErbB-2* / metabolism
  • Receptors, Estrogen* / metabolism
  • Receptors, Progesterone* / metabolism
  • Risk Assessment

Substances

  • Receptor, ErbB-2
  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • ERBB2 protein, human
  • Ki-67 Antigen