2015/05/19 by Céline Gérard, Mélanie Mestdagt, Ekaterine Tskitishvili +8 · 2 citations
Biochemistry, Genetics and Molecular Biology · Medicine · #Estrogen and related hormone effects #Menopause: Health Impacts and Treatments #Cancer, Lipids, and Metabolism
paper · doi:10.18632/oncotarget.4184
openalex publication_date 2015/05/19 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
// Céline Gérard 1 , Mélanie Mestdagt 1 , Ekaterine Tskitishvili 1 , Laudine Communal 2 , Anne Gompel 2,3 , Elisabete Silva 4 , Jean-François Arnal 5 , Françoise Lenfant 5 , Agnès Noel 1 , Jean-Michel Foidart 1 and Christel Péqueux 1 1 Laboratory of Tumor and Development Biology, GIGA-Cancer, University of Liège, Liège, Belgium 2 Gynaecological Endocrinology Unit, Paris Descartes University, Hôpitaux Universitaires, Paris, France 3 INSERM U 938, UPMC, Paris 4 Institute of Environment, Health and Societies, Brunel University London, UB83PH Uxbridge, United Kingdom 5 INSERM U1048, Institut des Maladies Métaboliques et Cardiovasculaires, University of Toulouse, UPS, Toulouse, France Correspondence to: Christel Péqueux, email: // Keywords : estetrol, menopause, breast cancer, estrogen receptor, SERM Received : March 03, 2015 Accepted : May 02, 2015 Published : May 19, 2015 Abstract Increased risk of breast cancer is a critical side effect associated with the use of a menopausal hormone therapy (MHT). Estetrol (E4) is a natural estrogen produced by the human fetal liver and is a promising compound for clinical use in MHT. However, its impact on breast cancer is controversial and poorly defined. In this preclinical study, we show that E4 acts as a weak estrogen by stimulating the growth of hormone-dependent breast cancer only at concentrations exceeding menopausal therapeutic needs. E4 presents also an antitumor activity by decreasing the strong proliferative effect of estradiol (E2). While estrogen receptor alpha (ERα) is the predominant receptor mediating its effects, the dual weak-estrogenic/anti-estrogenic feature of E4 results from differential signaling pathways activation. Both nuclear and rapid extra-nuclear signaling pathway are necessary for a complete estrogenic effect of E4. However, the antitumor action of E4 is not due to a capacity to antagonize E2-induced nuclear activity. Altogether, our results highlight that E4 has a limited impact on breast cancer and may offer a safe therapeutic window for the treatment of menopausal symptoms.