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

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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.

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Funding

The present work was supported by the Italian Association for Cancer Research (“Associazione Italiana per la Ricerca sul Cancro”, AIRC; MFAG 2020 ID 24698) and the Italian Ministry of Health (5 x 1000 funds 2017).

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Authors and Affiliations

  1. Medical Oncology 2, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Francesca Poggio, Tommaso Ruelle, Paolo Pronzato & Marco Tagliamento

  2. Breast Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Lucia Del Mastro

  3. Department of Internal Medicine and Medical Specialties (Di.M.I.), School of Medicine, University of Genova, Genova, Italy

    Lucia Del Mastro, Matteo Lambertini & Marco Tagliamento

  4. Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Marco Bruzzone & Marcello Ceppi

  5. U.O. Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Maria Grazia Razeti & Matteo Lambertini

  6. Department of Surgical Sciences and Integrated Diagnostic (DISC), School of Medicine, University of Genova, Genova, Italy

    Piero Fregatti

  7. Breast Surgery Clinic, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Piero Fregatti

  8. Physiopathology of Human Reproduction Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Claudia Massarotti

  9. Department of Medical Oncology, Gustave Roussy, Villejuif, France

    Maria Alice Franzoi

Authors
  1. Francesca Poggio
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  2. Lucia Del Mastro
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  3. Marco Bruzzone
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  4. Marcello Ceppi
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  5. Maria Grazia Razeti
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  6. Piero Fregatti
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  7. Tommaso Ruelle
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  9. Claudia Massarotti
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  10. Maria Alice Franzoi
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  11. Matteo Lambertini
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  12. Marco Tagliamento
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Corresponding author

Correspondence to Matteo Lambertini.

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Conflict of interest

F.P. declares honoraria and non-financial support from MSD, Eli Lilly, and Novartis outside the submitted work; L.D.M. declares honoraria and non-financial support from Roche, Novartis, Pfizer, MSD, Genomic Health, Takeda, Ipsen, Eisai, Eli Lilly, Celgene, Pierre Fabre, Seagen, Daiichi Sankyo, Exact Sciences, and Amgen outside the submitted work; M.L. declares personal fees from Roche, Novartis, Pfizer, Lilly, Takeda, AstraZeneca, Ipsen, Exact Sciences and Sandoz outside the submitted work; M.T. declares travel, accommodations, and expenses supported by Roche, Bristol-Myers Squibb, AstraZeneca, and Takeda, and activity as a medical writer supported by Novartis and Amgen. All other authors report no disclosures.

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Poggio, F., Del Mastro, L., Bruzzone, M. et al. Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis. Breast Cancer Res Treat 191, 269–275 (2022). https://doi.org/10.1007/s10549-021-06436-9

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  • DOI: https://doi.org/10.1007/s10549-021-06436-9

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