Abstract

Clinicians need to predict the number of involved nodes in breast cancer patients in order to ascertain severity, prognosis, and design subsequent treatment. The distribution of involved nodes often displays over-dispersion-a larger variability than expected. Until now, the negative binomial model has been used to describe this distribution assuming that over-dispersion is only due to unobserved heterogeneity. The distribution of involved nodes contains a large proportion of excess zeros (negative nodes), which can lead to over-dispersion. In this situation, alternative models may better account for over-dispersion due to excess zeros. This study examines data from 1152 patients who underwent axillary dissections in a tertiary hospital in India during January 1993-January 2005. We fit and compare various count models to test model abilities to predict the number of involved nodes. We also argue for using zero inflated models in such populations where all the excess zeros come from those who have at some risk of the outcome of interest. The negative binomial regression model fits the data better than the Poisson, zero hurdle/inflated Poisson regression models. However, zero hurdle/inflated negative binomial regression models predicted the number of involved nodes much more accurately than the negative binomial model. This suggests that the number of involved nodes displays excess variability not only due to unobserved heterogeneity but also due to excess negative nodes in the data set. In this analysis, only skin changes and primary site were associated with negative nodes whereas parity, skin changes, primary site and size of tumor were associated with a greater number of involved nodes. In case of near equal performances, the zero inflated negative binomial model should be preferred over the hurdle model in describing the nodal frequency because it provides an estimate of negative nodes that are at "high-risk" of nodal involvement.

Highlights

  • Accurate prediction of the number of involved nodes in breast cancer patients helps in grading severity of disease, avoid extensive axillary surgery dissections and assists with treatment decisions such as the use of neoadjuvant chemotherapy [1,2]

  • Another study showed that the negative binomial model provides a better fit as compared to the Poisson model for the total number of involved nodes in breast cancer patients in a meta-analysis [4]

  • We arguably demonstrate that the zero inflated models have an added advantage over the former in describing the event of interest in relation to the disease process itself, including identification of the factors involved in predicting the disease onset and disease progression

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Summary

Introduction

Accurate prediction of the number of involved nodes in breast cancer patients helps in grading severity of disease, avoid extensive axillary surgery dissections and assists with treatment decisions such as the use of neoadjuvant chemotherapy [1,2]. Only two studies have tried to predict the number of involved nodes in breast cancer patients. Guern and Vinh-Hung [3] found that a negative binomial model describes the number of nodal involvement better than the Poisson model due to excess variability, a condition called over-dispersion. Another study showed that the negative binomial model provides a better fit as compared to the Poisson model for the total number of involved nodes in breast cancer patients in a meta-analysis [4]. These studies used a negative binomial model, which posited that the over-dispersion occurred entirely due to unobserved heterogeneity and/or nodal clustering

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