{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T00:42:24Z","timestamp":1787964144330,"version":"build-2784847793"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T00:00:00Z","timestamp":1621468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Li\u00e8ge","award":["FSR-F-M-19\/6761"],"award-info":[{"award-number":["FSR-F-M-19\/6761"]}]},{"name":"University of Li\u00e8ge","award":["FSR-F-M-18\/4204"],"award-info":[{"award-number":["FSR-F-M-18\/4204"]}]},{"name":"University of Li\u00e8ge","award":["FSR-F-M-17\/1042"],"award-info":[{"award-number":["FSR-F-M-17\/1042"]}]},{"name":"University of Li\u00e8ge","award":["FSRC-S-SS-16\/05"],"award-info":[{"award-number":["FSRC-S-SS-16\/05"]}]},{"name":"Belgium National Fund for Scientific Research (FNRS)","award":["CDR-J.0131.19"],"award-info":[{"award-number":["CDR-J.0131.19"]}]},{"name":"Belgium National Fund for Scientific Research (FNRS)","award":["CDR-J.0197.17"],"award-info":[{"award-number":["CDR-J.0197.17"]}]},{"name":"FNRS-T\u00e9l\u00e9vie","award":["7.6526.18F"],"award-info":[{"award-number":["7.6526.18F"]}]},{"name":"FNRS-T\u00e9l\u00e9vie","award":["7.4597.16"],"award-info":[{"award-number":["7.4597.16"]}]},{"name":"SPW Economie, Emploi, Recherche (Belgium)"},{"name":"Fondation L\u00e9on Fr\u00e9d\u00e9ricq","award":["2016-2021"],"award-info":[{"award-number":["2016-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Given the unequivocal benefits of menopause hormone therapies (MHT) and combined oral contraceptives (COC), there is a clinical need for new formulations devoid of any risk of breast cancer promotion. Accumulating data from preclinical and clinical studies support that estetrol (E4) is a promising natural estrogen for MHT and COC. Nevertheless, we report here that E4 remains active on the endometrium, even under a dose that is neutral on breast cancer growth and lung metastasis dissemination. This implies that a progestogen should be combined with E4 to protect the endometrium of non-hysterectomized women from hyperplasia and cancer. Through in vivo observations and transcriptomic analyses, our work provides evidence that combining a progestogen to E4 is neutral on breast cancer growth and dissemination, with very limited transcriptional impact. The assessment of breast cancer risk in patients during the development of new MHT or COC is not possible given the requirement of long-term studies in large populations. This translational preclinical research provides new evidence that a therapeutic dose of E4 for MHT or COC, combined with progesterone or drospirenone, may provide a better benefit\/risk profile towards breast cancer risk compared to hormonal treatments currently available for patients.<\/jats:p>","DOI":"10.3390\/cancers13102486","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T06:13:45Z","timestamp":1621491225000},"page":"2486","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Estetrol Combined to Progestogen for Menopause or Contraception Indication Is Neutral on Breast Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Anne","family":"Gallez","sequence":"first","affiliation":[{"name":"Laboratory of Biology, Tumors and Development, GIGA-Cancer, University of Li\u00e8ge, 4000 Li\u00e8ge, 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Unit, GIGA-In Silico Medicine, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Primac","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Tumors and Development, GIGA-Cancer, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"G\u00e9rard","sequence":"additional","affiliation":[{"name":"Mithra Pharmaceuticals, rue Saint-Georges 5\/7, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lanie","family":"Taziaux","sequence":"additional","affiliation":[{"name":"Mithra Pharmaceuticals, rue Saint-Georges 5\/7, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7639-6310","authenticated-orcid":false,"given":"Ren\u00e9","family":"Houtman","sequence":"additional","affiliation":[{"name":"Precision Medicine Lab, 5349 AB Oss, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8180-1445","authenticated-orcid":false,"given":"Liesbet","family":"Geris","sequence":"additional","affiliation":[{"name":"Biomechanics Research Unit, GIGA-In Silico Medicine, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7oise","family":"Lenfant","sequence":"additional","affiliation":[{"name":"INSERM U1048, Institut des Maladies Me\u0301taboliques et Cardiovasculaires, University Paul Sabatier, 31432 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabetta","family":"Marangoni","sequence":"additional","affiliation":[{"name":"Translational Research Department, Institute Curie, PSL Research University, 75248 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9962-9236","authenticated-orcid":false,"given":"Nor Eddine","family":"Sounni","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Tumors and Development, GIGA-Cancer, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Michel","family":"Foidart","sequence":"additional","affiliation":[{"name":"Laboratory of Biology, Tumors and Development, GIGA-Cancer, University of Li\u00e8ge, 4000 Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"No\u00ebl","sequence":"additional","affiliation":[{"name":"Laboratory of 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