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SHR Neuro Cancer Cardio Lipid Metab Microb
Singer, CF; Bennink, HJ; Natter, C; Steurer, S; Rudas, M; Moinfar, F; Appels, N; Visser, M; Kubista, E.
Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer.
Carcinogenesis. 2014; 35(11):2447-2451
Doi: 10.1093/carcin/bgu144
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- Co-authors Med Uni Graz
- Moinfar Farid
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- Abstract:
- Estetrol (E4) is a fetal estrogen with estrogenic effects on reproductive organs and bone in preclinical models and in postmenopausal women. However, E4 exerts antiestrogenic effects on breast cancer (BC) cell growth in vitro and in vivo. We have investigated the effect of 14 days preoperative treatment with 20mg E4 per day on tumor proliferation markers, sex steroid receptor expression and endocrine parameters in a prospective, randomized, placebo-controlled, preoperative window trial in 30 pre- and post-menopausal women with estrogen-receptor positive early BC. E4 had a significant pro-apoptotic effect on tumor tissue, whereas Ki67 expression remained unchanged in both pre- and post-menopausal women. E4 increased sex-hormone-binding globulin significantly thereby reducing the concentrations of bioavailable estradiol. Follicle-stimulating hormone levels decreased in postmenopausal women only and luteinizing hormone levels remained unchanged. Systemic insulin growth factor-1 levels decreased significantly. Intratumoral epithelial ERα expression decreased significantly and a trend was found towards an increased expression of ERβ. This clinical data support the preclinical findings that E4 has antiestrogenic effects on BC cells, whereas earlier studies have shown that E4 has estrogenic effects on reproductive tissues and bone. Further clinical studies seem acceptable and are needed to confirm the safety and efficacy of E4 for the breast in hormone replacement therapy, including hormone replacement therapy in women who have or have had BC, especially in those BC patients treated with aromatase inhibitors and suffering from serious complaints due to estrogen deficiency. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
- Find related publications in this database (using NLM MeSH Indexing)
- Adult -
- Aged -
- Breast Neoplasms - drug therapy
- Breast Neoplasms - genetics
- Breast Neoplasms - pathology
- Breast Neoplasms - surgery
- Estetrol - administration & dosage
- Estrogen Receptor alpha - genetics
- Estrogen Receptor alpha - metabolism
- Female -
- Follicle Stimulating Hormone - biosynthesis
- Gene Expression Regulation, Neoplastic - drug effects
- Hormone Replacement Therapy -
- Humans -
- Insulin-Like Growth Factor I - biosynthesis
- Ki-67 Antigen - biosynthesis
- Middle Aged -
- Preoperative Period -