title: Qualitative assessment of the progesterone receptor and HER2 improves the Nottingham Prognostic Index up to 5 years after breast cancer diagnosis.
abstract: OBJECTIVE
  To investigate whether the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) can improve the Nottingham Prognostic Index (NPI) in the classification of patients with primary operable breast cancer for disease-free survival (DFS).
  
  
  METHODS
  The analysis is based on 1,927 patients with breast cancer treated between 2000 and 2005 at the University Hospitals, Leuven. We compared performances of NPI with and without ER, PR and/or HER2. Validation was done on two external data sets containing 862 and 2,805 patients from Oslo (Norway) and Auckland (New Zealand), respectively.
  
  
  RESULTS
  In the Leuven cohort, median follow-up was 66 months, and 13.7% of patients experienced a breast cancer-related event. Positive staining for ER, PR, and HER2 was detected, respectively, in 86.9%, 75.5%, and 11.9% of patients. Based on multivariate Cox regression modeling, the improved NPI (iNPI) was derived as NPI - PR positivity + HER2 positivity. Validation results showed a risk group reclassification of 20% to 30% of patients when using iNPI with its optimal risk boundaries versus NPI, in a majority of patients to more appropriate risk groups. An additional 10% of patients were classified into the extreme risk groups, where clinical actions are less ambiguous. Survival curves of reclassified patients resembled more closely those for patients in the same iNPI group than those for patients in the same NPI group.
  
  
  CONCLUSIONS
  The addition of PR and HER2 to NPI increases its 5-year prognostic accuracy. The iNPI can be considered as a clinically useful tool for stratification of patients with breast cancer receiving standard of care.
authors: Department of Electrical Engineering, Katholieke Universiteit Leuven, Kasteelpark Arenber, 10/2446, B-3001 Leuven, Belgium. vanya.vanbelle@esat.kuleuven.be
authors: Vanya
authors: V
authors: Van Belle
authors: Ben
authors: B
authors: Van Calster
authors: Olivier
authors: O
authors: Brouckaert
authors: Isabelle
authors: I
authors: Vanden Bempt
authors: Saskia
authors: S
authors: Pintens
authors: Vernon
authors: V
authors: Harvey
authors: Paula
authors: P
authors: Murray
authors: Björn
authors: B
authors: Naume
authors: Gro
authors: G
authors: Wiedswang
authors: Robert
authors: R
authors: Paridaens
authors: Philippe
authors: P
authors: Moerman
authors: Frederic
authors: F
authors: Amant
authors: Karin
authors: K
authors: Leunen
authors: Ann
authors: A
authors: Smeets
authors: Maria
authors: M
authors: Drijkoningen
authors: Hans
authors: H
authors: Wildiers
authors: Marie-Rose
authors: MR
authors: Christiaens
authors: Ignace
authors: I
authors: Vergote
authors: Sabine
authors: S
authors: Van Huffel
authors: Patrick
authors: P
authors: Neven
mesh_terms: D000368:Aged; D001530:Belgium; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D001943:Breast Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D006305:Health Status Indicators; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009520:New Zealand; D009664:Norway; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human