Antiestrogenic effects of the fetal estrogen estetrol in women with estrogen-receptor positive early breast cancer.

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.
AuthorsChristian F Singer, Herjan J T Coelingh Bennink, Camilla Natter, Stefan Steurer, Margaretha Rudas, Farid Moinfar, Nicole Appels, Monique Visser, Ernst Kubista
JournalCarcinogenesis (Carcinogenesis) Vol. 35 Issue 11 Pg. 2447-51 (Nov 2014) ISSN: 1460-2180 [Electronic] England
PMID24997853 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
Copyright© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Chemical References
  • Estrogen Receptor alpha
  • Ki-67 Antigen
  • Insulin-Like Growth Factor I
  • Follicle Stimulating Hormone
  • Estetrol
  • Adult
  • Aged
  • Breast Neoplasms (drug therapy, genetics, pathology, surgery)
  • Estetrol (administration & dosage)
  • Estrogen Receptor alpha (genetics, 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

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