title: Prognostic stratification of oestrogen receptor-positive HER2-negative lymph node-negative class of breast cancer.
abstract: OBJECTIVE
  Multigene assay is recommended currently for prognostic stratification of the clinically indeterminate group of breast cancer (BC) patients defined as lymph node (LN)-negative, oestrogen receptor (ER)-positive, HER2-negative (LN-/ER+/HER2-) to determine the use of chemotherapy. However, this cohort, comprising approximately 40% of BC, is not a homogeneous group and shows variable outcome. This study aims to determine the prognostic value of routinely assessed variables, singly and in combination, in LN-/ER+/HER2-BC patients.
  
  
  RESULTS
  A total of 830 LN-/ER+/HER2-chemotherapy-naive BCs were investigated. The prognostic value of histological grade, tumour size, lymphovascular invasion (LVI), progesterone receptor (PgR) and Ki67 labelling index (Ki67LI) was assessed. In this series, only 25% of patients received hormone therapy. Median follow-up was 172 months. In the whole cohort, tumour grade, size, LVI, PgR and Ki67LI were correlated highly with outcome in a time-dependent manner. The outcome of this group varied widely from 97% (20% of cases) to 50% survival rate after 10-year follow-up using a combination of these markers. A prognostic index (Nottingham Px) incorporating grade, size, PgR and Ki67LI, was developed. The index can stratify the whole cohort robustly as well as the higher-risk subgroup (NPI score >3.4) into distinct prognostic classes.
  
  
  CONCLUSIONS
  Current routinely assessed variables can provide additional prognostic information in LN-/ER+/HER2-BC. The proposed (Nottingham Px) index can stratify the BC clinically indeterminate group of patients into excellent and poor prognostic subgroups and can be used to identify reliably patients for systemic chemotherapy or further multigene prognostic testing. Performance of prognostic variables in these tumours is time-dependent, and should be considered in future studies.
authors: Departments of Histopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Emad A
authors: EA
authors: Rakha
authors: John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
authors: Devika
authors: D
authors: Agarwal
authors: Departments of Histopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Andrew R
authors: AR
authors: Green
authors: Molecular Diagnostics and Personalised Therapeutics Unit, University of Ha'il, Ha'il, Saudi Arabia.
authors: Ibraheem
authors: I
authors: Ashankyty
authors: Departments of Histopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors: Ian O
authors: IO
authors: Ellis
authors: John van Geest Cancer Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, UK.
authors: Graham
authors: G
authors: Ball
authors: Departments of Histopathology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham and Nottingham University Hospitals NHS Trust, Nottingham, UK.|Molecular Diagnostics and Personalised Therapeutics Unit, University of Ha'il, Ha'il, Saudi Arabia.
authors: Mohammed A
authors: MA
authors: Alaskandarany
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; C508053:ERBB2 protein, human
keywords: Oncotype DX; breast carcinoma; prognostic classifications; routine practice