Influence of Competing Risks on Estimates of Recurrence Risk and Breast Cancer-specific Mortality in Analyses of the Early Breast Cancer Trialists Collaborative Group

Sci Rep. 2020 Mar 5;10(1):4091. doi: 10.1038/s41598-020-61093-0.

Abstract

Early-stage breast cancer (BC) is a curable disease with many patients dying of causes other than BC. The influence of non-BC death and other competing risks on the interpretation of Kaplan-Meier (KM)-based analyses for BC-specific outcomes are unknown. We searched the Oxford University website to identify all meta-analyses published by the Early Breast Cancer Trialists Collaborative Group (EBCTCG) between 2005 and 2018. The potential influence of competing risks was estimated using a validated multivariable linear model that predicts the difference between KM and cumulative incidence function (CIF) on estimates of BC-specific outcomes. The initial search identified 14 EBCTCG papers, 10 (71%) reported data on BC and competing events. Eight (80%) had a relative difference between KM and the competing risk adjusted estimates exceeding 10%. The median relative difference was 28.4% for local-recurrence; 16.8% for distant-recurrence, and 6.7% for BC-specific mortality. There was a 18.9% relative difference between KM and CIF adjusted analyses beyond 10 years. The use of KM-based methods when competing risks are present biases risk estimates in studies of early BC especially for uncommon outcomes such as local recurrence. The use of CIF to calculate BC-specific outcomes may be preferable in this setting.

MeSH terms

  • Breast Neoplasms / epidemiology
  • Breast Neoplasms / mortality*
  • Breast Neoplasms / pathology
  • Canada / epidemiology
  • Female
  • Humans
  • Incidence
  • Models, Statistical*
  • Neoplasm Recurrence, Local / epidemiology
  • Neoplasm Recurrence, Local / mortality*
  • Neoplasm Recurrence, Local / pathology
  • Prognosis
  • Risk Assessment / methods*
  • Survival Rate