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Article Open Access

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

  • Authors:
    • Javier Angel Canelas Fernández
    • Jéssica Alonso‑Molero
    • Paz Rodríguez‑Cundín
    • Javier Llorca
    • Inés Gómez‑Acebo
    • Trinidad Dierssen‑Sotos
  • View Affiliations / Copyright

    Affiliations: Department of Medical and Surgical Sciences, Area of Preventive Medicine and Public Health, University of Cantabria, 39011 Santander, Spain, Service of Preventive Medicine, Hospital Universitario Marqués de Valdecilla, 39008 Santander, Spain
    Copyright: © Canelas Fernández et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 262
    |
    Published online on: April 24, 2026
       https://doi.org/10.3892/ol.2026.15617
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Abstract

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.
View Figures

Figure 1

Flowchart.

Figure 2

Risk of bias in non-randomized
studies.

Figure 3

Forest plot of the association
between hormone replacement therapy use and breast cancer
mortality. exp(ES), exponentiated effect size (expressed as odds
ratio); LNN, lymph node negative; LNP, lymph node positive.

Figure 4

Forest plot of the association
between HRT use and breast cancer mortality based on HRT duration.
exp(ES), exponentiated effect size (expressed as odds ratio); HRT,
hormone replacement therapy; LNN, lymph node negative; LNP, lymph
node positive.

Figure 5

Forest plot of the association
between HRT use and breast cancer mortality based on the status of
HRT use at the time of diagnosis. exp(ES), exponentiated effect
size (expressed as odds ratio); HRT, hormone replacement therapy;
LNN, lymph node negative; LNP, lymph node positive.

Figure 6

Forest plot of the association
between hormone replacement therapy use and breast cancer mortality
categorized by recruitment period. exp(ES), exponentiated effect
size (expressed as odds ratio); LNN, lymph node negative; LNP,
lymph node positive.
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Copy and paste a formatted citation
Spandidos Publications style
Canelas Fernández J, Alonso‑Molero J, Rodríguez‑Cundín P, Llorca J, Gómez‑Acebo I and Dierssen‑Sotos T: Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis. Oncol Lett 31: 262, 2026.
APA
Canelas Fernández, J., Alonso‑Molero, J., Rodríguez‑Cundín, P., Llorca, J., Gómez‑Acebo, I., & Dierssen‑Sotos, T. (2026). Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis. Oncology Letters, 31, 262. https://doi.org/10.3892/ol.2026.15617
MLA
Canelas Fernández, J., Alonso‑Molero, J., Rodríguez‑Cundín, P., Llorca, J., Gómez‑Acebo, I., Dierssen‑Sotos, T."Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis". Oncology Letters 31.6 (2026): 262.
Chicago
Canelas Fernández, J., Alonso‑Molero, J., Rodríguez‑Cundín, P., Llorca, J., Gómez‑Acebo, I., Dierssen‑Sotos, T."Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis". Oncology Letters 31, no. 6 (2026): 262. https://doi.org/10.3892/ol.2026.15617
Copy and paste a formatted citation
x
Spandidos Publications style
Canelas Fernández J, Alonso‑Molero J, Rodríguez‑Cundín P, Llorca J, Gómez‑Acebo I and Dierssen‑Sotos T: Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis. Oncol Lett 31: 262, 2026.
APA
Canelas Fernández, J., Alonso‑Molero, J., Rodríguez‑Cundín, P., Llorca, J., Gómez‑Acebo, I., & Dierssen‑Sotos, T. (2026). Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis. Oncology Letters, 31, 262. https://doi.org/10.3892/ol.2026.15617
MLA
Canelas Fernández, J., Alonso‑Molero, J., Rodríguez‑Cundín, P., Llorca, J., Gómez‑Acebo, I., Dierssen‑Sotos, T."Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis". Oncology Letters 31.6 (2026): 262.
Chicago
Canelas Fernández, J., Alonso‑Molero, J., Rodríguez‑Cundín, P., Llorca, J., Gómez‑Acebo, I., Dierssen‑Sotos, T."Effect of the use of hormonal replacement therapy on breast cancer prognosis: A systematic review and meta‑analysis". Oncology Letters 31, no. 6 (2026): 262. https://doi.org/10.3892/ol.2026.15617
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