This prospective study assessed the endometrial effects of fulvestrant, a pure estrogen-receptor antagonist, in postmenopausal women with breast cancer. This single-center study enrolled postmenopausal patients who had an intact uterus at baseline with progressive metastatic breast cancer on tamoxifen followed by an oral aromatase inhibitor (AI). Fulvestrant (250 mg) was administered every 28 ± 3 days via IM injection. Transvaginal ultrasonography (TVUS) was performed at baseline and after 3 months of therapy. Primary and secondary endpoints were changes from baseline in double endometrial thickness (DET) and uterine volume (UV), respectively. No interventions were performed on any asymptomatic uterine abnormalities that were detected at baseline. In total, 32 women were enrolled. Five patients had no repeat TVUS because of early progression before 3 months, leaving 27 evaluable patients for final analysis. After 3 months therapy, mean DET had significantly decreased by 23.08% (P = 0.010). Mean UV also decreased by 10.88%, although this change was not significant (P = 0.119). After 3 months of therapy, none reported vaginal bleeding, there were no changes noted in most of the uterine pathologies present at baseline and no new uterine abnormalities were detected. We observed that 3 months of fulvestrant treatment resulted in a significant decrease in endometrial growth and a non-significant decrease in UV in postmenopausal women with metastatic breast cancer previously exposed to tamoxifen and AIs. Furthermore, no new uterine pathologies were detected, indicating that fulvestrant behaves as a pure antiestrogen at the uterine level.
Breast cancer Endometrium Fulvestrant Hormonal therapy Ultrasonography Uterus
This is a preview of subscription content, log in to check access.
We thank all the physicians, trial nurses, pharmacists and secretaries who assisted us and most especially the patients who kindly agreed to participate in this study. This research was conducted with support from the Investigator-Sponsored Study Program of AstraZeneca. AstraZeneca kindly provided fulvestrant (Faslodex) for the study patients, but was not involved in the study design, in the collection, analysis, and interpretation of data, in the writing of the manuscript nor in the decision to submit the manuscript for publication. AstraZeneca provided an unrestricted grant which was used for a Ph.D. stipend (LM).
Fisher B, Constantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer. Report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90:1371–1388. doi:10.1093/jnci/90.18.1371PubMedCrossRefGoogle Scholar
Poole R, Paridaens R (2007) The use of third-generation aromatase inhibitors and tamoxifen in the adjuvant treatment of postmenopausal patients with hormone-dependent breast cancer: evidence based review. Curr Opin Oncol 19:564–572PubMedCrossRefGoogle Scholar
Morales L, Timmerman D, Neven P et al (2005) Third generation aromatase inhibitors may prevent endometrial growth and reverse tamoxifen-induced uterine changes in postmenopausal breast cancer patients. Ann Oncol 16:70–74. doi:10.1093/annonc/mdi021PubMedCrossRefGoogle Scholar
Garrone O, Mezi S, Occelli M (2003) Reversal of tamoxifen induced endometrial modifications by switching to letrozole in early breast cancer patients: a prospective TVUS study. Ann Oncol 14:s22Google Scholar
Duffy S, Jackson TL, Lansdown M et al (2006) The ATAC (‘Arimidex’, Tamoxifen, Alone or in Combination) adjuvant breast cancer trial: first results of the endometrial sub-protocol following 2 years of treatment. Hum Reprod 21:545–553. doi:10.1093/humrep/dei322PubMedCrossRefGoogle Scholar
Markovitch O, Tepper R, Fishman A et al (2007) Aromatase inhibitors reverse tamoxifen induced endometrial ultrasonographic changes in postmenopausal breast cancer patients. Breast Cancer Res Treat 101:185–190. doi:10.1007/s10549-006-9285-xPubMedCrossRefGoogle Scholar
Bertelli G, Hall E, Ireland E et al (2007) Endometrial status in the Intergroup Exemestane Study (IES) up to 2 years post-treatment. Breast Cancer Res Treat 106:s111Google Scholar
Kieback DG, Harbeck N, Bauer W et al (2008) Endometrial safety of cross-over treatment with tamoxifen followed by exemestane. Eur J Cancer 6:s198Google Scholar
Boruban MC, Altundag K, Kilic GS, Blankstein J (2008) From endometrial hyperplasia to endometrial cancer: insight into the biology and possible medical preventive measures. Eur J Cancer Prev 17:133–138PubMedCrossRefGoogle Scholar
Perey L, Paridaens R, Hawle H et al (2007) Clinical benefit of fulvestrant in postmenopausal women with advanced breast cancer and primary or acquired resistance to aromatase inhibitors: final results of phase II Swiss Group for Clinical Cancer Research Trial (SAKK 21/00). Ann Oncol 18:64–69. doi:10.1093/annonc/mdl341PubMedCrossRefGoogle Scholar
Chia S, Gradishar W, Mauriac L et al (2008) Double-blind, randomized placebo controlled trial of fulvestrant compared with exemestane after prior non-steroidal aromatase inhibitor therapy in postmenopausal women with hormone receptor-positive, advanced breast cancer: results from EFECT. J Clin Oncol 26:1664–1670. doi:10.1200/JCO.2007.13.5822PubMedCrossRefGoogle Scholar
Gaducci A, Cosio S, Genazzani AR (2004) Use of estrogen antagonists and aromatase inhibitors in breast cancer and hormonally sensitive tumors of the uterine body. Curr Opin Investig Drugs 5:1031–1044Google Scholar
Addo S, Yates RA, Laight A (2002) A phase I trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestrant on the endometrium in healthy postmenopausal volunteers. Br J Cancer 87:1354–1359. doi:10.1038/sj.bjc.6600644PubMedCrossRefGoogle Scholar
Donnez J, Vivancos BH, Kudela M et al (2003) A randomized, placebo-controlled, dose-ranging trial comparing fulvestrant with goserelin in premenopausal patients with uterine fibroids awaiting hysterectomy. Fertil Steril 79:1380–1389. doi:10.1016/S0015-0282(03)00261-9PubMedCrossRefGoogle Scholar