Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis

Breast cancer is a global health concern. Hormone replacement therapy (HRT) prior to breast cancer diagnosis is of particular interest due to the hormone sensitivity of the breasts. Previous evidence has altered the perception of HRT by highlighting that certain risks could outweigh the benefits. As a result, the popularity of HRT for menopausal symptom relief and disease prevention decreased. To investigate the relationship between pre‑diagnosis HRT use and breast cancer survival, a meta‑analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta‑Analyses guidelines. A comprehensive search across MEDLINE, Cochrane and Web of Science databases up to August 2025 identified 33 studies. These studies evaluated the impact of HRT on breast cancer survival utilizing various study designs. Quality assessment was performed using the Newcastle Ottawa Scale, while the Risk of Bias in Non‑Randomized Studies of Exposures tool was used to evaluate the risk of bias. The pooled analysis revealed that HRT use prior to breast cancer diagnosis was associated with reduced breast cancer mortality (odds ratio, 0.86; 95% CI, 0.79‑0.94). Subgroup analyses based on duration and timing of HRT use at diagnosis revealed heterogeneous associations with survival. Shorter duration of use (<5 years) appeared to be associated with lower breast cancer mortality; however, these subgroup analyses were based on a limited number of studies and should be interpreted with caution. Longer duration of use (>10 years) showed no clear association. Studies recruiting after 2000 showed an inverse association between HRT use and breast cancer mortality, a trend more pronounced than in earlier years, although evidence remains limited. In conclusion, pre‑diagnosis HRT use was associated with improved breast cancer survival, influenced by treatment duration, timing and temporal factors. It is necessary to note that subgroup findings based on the treatment duration and recruitment period were limited by the low number of contributing studies and should be interpreted with caution. Despite methodological differences among the included studies, the present findings provide valuable insights into the complex relationship between HRT and breast cancer prognosis.