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Meta-Analysis
. 2022 Jan;191(2):269-275.
doi: 10.1007/s10549-021-06436-9. Epub 2021 Nov 3.

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis

Francesca Poggio  1 , Lucia Del Mastro  2   3 , Marco Bruzzone  4 , Marcello Ceppi  4 , Maria Grazia Razeti  5 , Piero Fregatti  6   7 , Tommaso Ruelle  1 , Paolo Pronzato  1 , Claudia Massarotti  8 , Maria Alice Franzoi  9 , Matteo Lambertini  10   11 , Marco Tagliamento  1   3
Affiliations
Meta-Analysis

Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis

Francesca Poggio et al. Breast Cancer Res Treat. 2022 Jan.

Abstract

Purpose: Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors.

Methods: A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status.

Results: Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12-1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15-2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80-1.77, p = 0.390).

Conclusion: Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Keywords: Breast cancer; Chemotherapy; Endocrine therapy; Hormone replacement therapy; Iatrogenic menopause.

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References

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