Combined estrogenic and anti-estrogenic properties of estetrol on breast cancer may provide a safe therapeutic window for the treatment of menopausal symptoms.
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| 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 (ERĪ±) 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.
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| Authors | Céline Gérard, Mélanie Mestdagt, Ekaterine Tskitishvili, Laudine Communal, Anne Gompel, Elisabete Silva, Jean-François Arnal, Françoise Lenfant, Agnès Noel, Jean-Michel Foidart, Christel Péqueux |
| Journal | Oncotarget (Oncotarget) Vol. 6 Issue 19 Pg. 17621-36 (Jul 10 2015) ISSN: 1949-2553 [Electronic] United States |
| PMID | 26056044 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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