Statistical analysis The characteristics of the patients with assessable data will be compared with X2 test or Wilcoxon rank-sum tests. Overall survival (OS) will be defined as duration from diagnosis of the metastasis to last visit or death. Progression free interval (PFI) will be defined as duration from diagnosis of the metastasis to the point when disease progression will be detected. Complete response (CR) will be achieved by a systemic therapy or no evidence of clinical disease (NED) after a local therapy considered relapse-free, and the duration between induction of relapse free status and the point of relapse detection will be defined as the relapse free interval (RFI); survival time after induction of relapse-free status without relapse will be defined as relapse free survival (RFS). Unrelated death other than from breast cancer will be considered as censored in evaluation of PFI and RFI. Survival curves will be calculated according to the Kaplan-Meier method. The log-rank test will be used to evaluate differences in survival between groups with intervention and no-intervention. A multivariate analysis will be performed by Cox regression and the following variables will be included: age, DFI, performance status (PS), liver metastasis, pulmonary metastasis, presence of other metastasis, hormone receptor status, HER2 status, Ki-67 status, intrinsic subtype, administration of local therapy, and chemotherapy regimens. Statistical significance will be defined as a p value <0.05. All p values will be calculated for two-sided analyses. For observed survival, all deaths will be considered as events including patients who died from secondary causes without recurrence. Statistical analyses will be performed using SPSS 22.0 (SPSS, Chicago, IL) software.