Hormone replacement therapy and breast cancer survival: a systematic review and meta-analysis of observational studies

Previous studies on the association between hormone replacement therapy (HRT) and breast cancer survival have yielded mixed results. We aimed to perform a meta-analysis to assess the association with all available studies. Relevant studies were identified by searching PubMed and EMBASE to April 2017. We calculated the summary hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects models. The dose-response relationship was assessed by random-effects meta-analysis and dose-response meta-regression models. Forty cohort studies and two case-control studies involving 1,756,833 participants were included. The results showed that prediagnosis HRT use was associated with decreased risk of dying from breast cancer (HR = 0.88, 95% CI 0.81-0.97) or any cause (HR = 0.79, 95% CI 0.69-0.90). Postdiagnosis HRT use also showed a beneficial effect on breast cancer survival. In the subgroup analyses, we found that patients who were current users at diagnosis or who received combined hormone therapy before diagnosis seemed to show more benefit from HRT use. In dose-response analysis, we observed a linear relationship between prediagnosis HRT and breast cancer-specific mortality and a 1-year increment in duration of exposure to HRT conferred an HR of 0.99 (95% CI 0.98-1.00) for death from breast cancer. In conclusion, the average effect of HRT use seems not harmful to breast cancer survival. Nevertheless, this effect of HRT use is needed for further assessment.