Development and validation of a new predictive model for breast cancer survival in New Zealand and comparison to the Nottingham prognostic index

Abstract

Background: The only available predictive models for the outcome of breast cancer patients in New Zealand (NZ) are based on data in other countries. We aimed to develop and validate a predictive model using NZ data for this population, and compare its performance to a widely used overseas model, the Nottingham Prognostic Index (NPI).

Methods: We developed a model to predict 10-year breast cancer-specific survival, using data collected prospectively in the largest population-based regional breast cancer registry in NZ (Auckland, 9182 patients), and assessed its performance in this data set (internal validation) and in an independent NZ population-based series of 2625 patients in Waikato (external validation). The data included all women with primary invasive breast cancer diagnosed from 1 June 2000 to 30 June 2014, with follow up to death or Dec 31, 2014. We used multivariate Cox proportional hazards regression to assess predictors and to calculate predicted 10-year breast cancer mortality, and therefore survival, probability for each patient. We assessed observed survival by the Kaplan Meier method. We assessed discrimination by the C statistic, and calibration by comparing predicted and observed survival rates for patients in 10 groups ordered by predicted 10-year survival. We compared this NZ model with the Nottingham Prognostic Index (NPI) in this validation data set.

Results: Discrimination was good: C statistics were 0.84 for internal validity and 0.83 for an independent external validity. For calibration, for both internal and external validity the predicted 10-year survival probabilities in all groups of patients, ordered by predicted survival, were within the 95% confidence intervals (CI) of the observed Kaplan-Meier survival probabilities. The NZ model showed good discrimination even within the prognostic groups defined by the NPI.

Conclusions: These results for the New Zealand model show good internal and external validity, transportability, and potential clinical value of the model, and its clear superiority over the NPI. Further research is needed to assess other potential predictors, to assess the model's performance in specific subgroups of patients, and to compare it to other models, which have been developed in other countries and have not yet been tested in NZ.

Keywords: Breast cancer; Mortality; New Zealand; Nottingham prognostic index; Predictive model; Prognosis; Survival.

Fig. 1

Internal validity: 10-year breast cancer specific survival as predicted by the NZ model (horizontal axis) for 10 groups of patients in the derivation data set (Auckland), grouped by predicted survival,compared to observed (Kaplan-Meier) survival and its 95% confidence limits (vertical axis). Line of identity between predicted and observed survival shown

Fig. 2

External validity: 10-year breast cancer specific survival as predicted by the NZ model (horizontal axis) for 8 groups of patients in the validation data set (Waikato), grouped by predicted survival, using Auckland derived model, compared to observed (Kaplan-Meier) survival and its 95% confidence limits (vertical axis). Line of identity between predicted and observed survival shown

Fig. 3

A nomogram of the fitted model, showing the relative contribution of variables to the model and also, by relative sizes of the boxes, the distribution of each. The distribution of the total score is also shown and the dots show a particular person with 10-year mortality risk of 2.5% (95% CI 1.3–3.6%)