Qualitative assessment of the progesterone receptor and HER2 improves the Nottingham Prognostic Index up to 5 years after breast cancer diagnosis.
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.
Van Belle
Vanya
V
Department of Electrical Engineering, Katholieke Universiteit Leuven, Kasteelpark Arenber, 10/2446, B-3001 Leuven, Belgium. vanya.vanbelle@esat.kuleuven.be
Van Calster
Ben
B
Brouckaert
Olivier
O
Vanden Bempt
Isabelle
I
Pintens
Saskia
S
Harvey
Vernon
V
Murray
Paula
P
Naume
Björn
B
Wiedswang
Gro
G
Paridaens
Robert
R
Moerman
Philippe
P
Amant
Frederic
F
Leunen
Karin
K
Smeets
Ann
A
Drijkoningen
Maria
M
Wildiers
Hans
H
Christiaens
Marie-Rose
MR
Vergote
Ignace
I
Van Huffel
Sabine
S
Neven
Patrick
P
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
D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human