nach oben

Erschienen in:

03.11.2021 | Review

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

verfasst von: Francesca Poggio, Lucia Del Mastro, Marco Bruzzone, Marcello Ceppi, Maria Grazia Razeti, Piero Fregatti, Tommaso Ruelle, Paolo Pronzato, Claudia Massarotti, Maria Alice Franzoi, Matteo Lambertini, Marco Tagliamento

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2022

Einloggen, um Zugang zu erhalten

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.

Nur mit Berechtigung zugänglich

Siegel RL, Miller KD, Fuchs HE, Jemal A (2021) Cancer statistics, 2021. CA Cancer J Clin 71:7–33. https://doi.org/10.3322/caac.21654CrossRefPubMed

Lambertini M, Peccatori FA, Demeestere I et al (2020) Fertility preservation and post-treatment pregnancies in post-pubertal cancer patients: ESMO Clinical Practice Guidelines†. Ann Oncol. https://doi.org/10.1016/j.annonc.2020.09.006CrossRefPubMed

The ESHRE Guideline Group on Female Fertility Preservation, Anderson RA, Amant F, et al (2020) ESHRE guideline: female fertility preservation†. Hum Reprod Open 2020:hoaa052. https://doi.org/10.1093/hropen/hoaa052

Franzoi MA, Agostinetto E, Perachino M et al (2021) Evidence-based approaches for the management of side-effects of adjuvant endocrine therapy in patients with breast cancer. Lancet Oncol. https://doi.org/10.1016/S1470-2045(20)30666-5CrossRefPubMed

Pistilli B, Paci A, Ferreira AR et al (2020) Serum detection of nonadherence to adjuvant tamoxifen and breast cancer recurrence risk. J Clin Oncol 38:2762–2772. https://doi.org/10.1200/JCO.19.01758CrossRefPubMedPubMedCentral

Grandi G, Caroli M, Cortesi L et al (2020) Postmenopausal hormone therapy in BRCA gene mutation carriers: to whom and which? Expert Opin Drug Saf 19:1025–1030. https://doi.org/10.1080/14740338.2020.1791818CrossRefPubMed

Gompel A, Kandouz M, Sirotnachkova M et al (1997) The effect of tibolone on proliferation, differentiation and apoptosis in normal breast cells. Gynecol Endocrinol 11:77–79. https://doi.org/10.3109/09513599709152586CrossRef

Valdivia I, Campodónico I, Tapia A et al (2004) Effects of tibolone and continuous combined hormone therapy on mammographic breast density and breast histochemical markers in postmenopausal women. Fertil Steril 81:617–623. https://doi.org/10.1016/j.fertnstert.2003.07.041CrossRefPubMed

Chlebowski RT, Anderson GL, Aragaki AK, et al (2020) Association of Menopausal Hormone Therapy With Breast Cancer Incidence and Mortality During Long-term Follow-up of the Women’s Health Initiative Randomized Clinical Trials. 12

10.

NCCN Clinical Practice Guidelines in Oncology, Breast Cancer - version 6.2020 - September 8 2020. Available at www.nccn.org/patients.

11.

Vassilopoulou-Sellin R, Cohen DS, Hortobagyi GN et al (2002) Estrogen replacement therapy for menopausal women with a history of breast carcinoma: Results of a 5-year, prospective study. Cancer 95:1817–1826. https://doi.org/10.1002/cncr.10913CrossRefPubMed

12.

Holmberg L, Iversen O-E, Rudenstam CM et al (2008) Increased risk of recurrence after hormone replacement therapy in breast cancer survivors. JNCI J Natl Cancer Inst 100:475–482. https://doi.org/10.1093/jnci/djn058CrossRefPubMed

13.

Kenemans P, Bundred NJ, Foidart J-M et al (2009) Safety and efficacy of tibolone in breast-cancer patients with vasomotor symptoms: a double-blind, randomised, non-inferiority trial. Lancet Oncol 10:135–146. https://doi.org/10.1016/S1470-2045(08)70341-3CrossRefPubMed

14.

Fahlén M, Fornander T, Johansson H et al (2013) Hormone replacement therapy after breast cancer: 10 year follow up of the Stockholm randomised trial. Eur J Cancer 49:52–59. https://doi.org/10.1016/j.ejca.2012.07.003CrossRefPubMed

15.

Marsden J, Whitehead M, A’Hern R et al (2000) Are randomized trials of hormone replacement therapy in symptomatic women with breast cancer feasible? Fertil Steril 73:292–299. https://doi.org/10.1016/S0015-0282(99)00510-5CrossRefPubMed

16.

Pagani O, Francis PA, Fleming GF et al (2020) Absolute improvements in freedom from distant recurrence to tailor adjuvant endocrine therapies for premenopausal women: results from TEXT and SOFT. J Clin Oncol 38:1293–1303. https://doi.org/10.1200/JCO.18.01967CrossRefPubMed

17.

Ferreira AR, Di Meglio A, Pistilli B et al (2019) Differential impact of endocrine therapy and chemotherapy on quality of life of breast cancer survivors: a prospective patient-reported outcomes analysis. Ann Oncol 30:1784–1795. https://doi.org/10.1093/annonc/mdz298CrossRefPubMed

18.

Chirgwin JH, Giobbie-Hurder A, Coates AS et al (2016) Treatment adherence and its impact on disease-free survival in the breast international group 1–98 trial of tamoxifen and letrozole, alone and in sequence. J Clin Oncol 34:2452–2459. https://doi.org/10.1200/JCO.2015.63.8619CrossRefPubMedPubMedCentral

19.

Collaborative Group on Hormonal Factors in Breast Cancer (2019) Type and timing of menopausal hormone therapy and breast cancer risk: individual participant meta-analysis of the worldwide epidemiological evidence. Lancet Lond Engl 394:1159–1168. https://doi.org/10.1016/S0140-6736(19)31709-XCrossRef

20.

van Barele M, Heemskerk-Gerritsen BAM, Louwers YV et al (2021) Estrogens and progestogens in triple negative breast cancer: do they harm? Cancers 13:2506. https://doi.org/10.3390/cancers13112506CrossRefPubMedPubMedCentral

Titel: Safety of systemic hormone replacement therapy in breast cancer survivors: a systematic review and meta-analysis
verfasst von: Francesca Poggio
Lucia Del Mastro
Marco Bruzzone
Marcello Ceppi
Maria Grazia Razeti
Piero Fregatti
Tommaso Ruelle
Paolo Pronzato
Claudia Massarotti
Maria Alice Franzoi
Matteo Lambertini
Marco Tagliamento
Publikationsdatum: 03.11.2021
Verlag: Springer US
Erschienen in: Breast Cancer Research and Treatment / Ausgabe 2/2022
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-021-06436-9

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

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