Analyzing Relationship Between Local and Metastasis Relapses with Survival of Patients with Breast Cancer: A Study Using Joint Frailty Model

Individuals with breast cancer may experience multiple types of recurrence and a terminal event during their life. Follow-up may be interrupted for several reasons, including patients lost to follow-up or end of a study. Death is considered as a dependent terminal event. The main objective was to model the dependency between (locoregional and metastaticrelapses and death in breast cancer patients. This retrospective cohort study was conducted in Cancer Research Center, Shahid Beheshti University of Medical Sciences on 342 patients with BC. Patients were followed up to 20 years from January 1996 until February 2015. This study considers the analysis of diseases recurrence and survival for joint modeling of three correlated evens: Local recurrence, metastasis, and death. The aims are to detect the effects of relapses on death and the correlation between local and distant recurrences. We propose a joint frailty model for multiple recurrent events with a terminal event. According to all obtained results of the fitted models, the risk of local and metastatic relapses or death increased for women with positive lymph node (N+) or for women with a grade higher than I. Also, it was found that if the association between these 3 times to events are not taken into account, we may lose a significant association. The variable HR+ was significantly correlated with the hazards of two types of recurrences, and death for both reduced and proposed models (P < 0.05). We concluded that the risk of locoregional recurrences is correlated with the risk of metastatic and the risk of metastatic relapse is also correlated with death. In this special setting, it can be difficult to get an independence between locoregional and distant recurrences. Also, these results should be considered with caution, with the few number of recurrences.