Multivariate Joint Frailty Models for Modeling Multiple Recurrent Events and Their Application in Breast Cancer

Background and Objective: Breast cancer is one of the most prevalent recurrent cancers among women. Several factors affecting multiple recurrences of this disease have been studied and recognized in various studies. However, despite the fact that these factors are known, it is not always possible to accurately predict the incidence of metastases. On the other hand, a simultaneous examination of different types of recurrences leads to the achievement of more accurate results. One of the various types of models used to analyze recurrent events considering the lack of homogeneity amongst patients is a frailty model. This study aimed to investigate an application of a joint frailty model for modeling multiple recurrences in data related to breast cancer patients. Materials and Methods: In this retrospective study, 342 patients with breast cancer whose records were registered for follow-up in a Cancer Research Center at Shohadaye Tajrish Hospital were investigated. These patients were monitored by this center for at least 6 months after diagnosis and their latest statuses were recorded. For data analysis, the joint frailty survival model was used. Running the model and conducting the data analysis were performed via the R statistical software. Results: Three-year and five-year survival rates for the patients were 0.79 and 0.68, respectively. Given the results obtained from a fitted joint frailty model, it can be stated that the risk of multiple recurrences (local and metastases) increased for the patients with tumor grades greater than I. Moreover, it was found that when neglecting the relationship between multiple recurrences in the patients with breast cancer, a significant correlation was missed.Conclusion: With regard to the significant variance of the frailty component of the metastases event, it can be inferred that patients with the same predictive variables are prone to different levels of metastases risk and, on the other hand, given the low frequency of types of recurrences in this study, caution should be exercised when considering the obtained results

Multivariate Joint Frailty Models for Modeling Multiple Recurrent Events and Their Application in Breast Cancer Keywords:

Breast Cancer , Joint Frailty Model , Multiple Recurrent Events , Metastases