A Prospective, Randomized Study to Compare Effects of Ulipristal Acetate with a Combined Oral Contraceptive on Breast Epithelial Cell Proliferation.

一项前瞻性随机研究，比较醋酸乌利司他与复方口服避孕药对乳腺上皮细胞增殖的影响。

• 批准号: 9307756
• 负责人: CAROLYN L WESTHOFF
• 金额: $ 49.5万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307756
• 关键词: Acetates; Adverse effects; Advisory Committees; Age; Anti-Progestin; Benefits and Risks; Breast; Breast Cancer Prevention; Breast Epithelial Cells; Breast biopsy; Categories; Cell Proliferation; Chemoprevention; Chemopreventive Agent; Clinical Trials; Contraceptive Agents; Contraceptive Usage; Diagnosis; Disease; Dose; Endometrial Carcinoma; Endometrium; Epidemiology; Estrogens; Evaluation; Exposure to; Future; Hormones; Luteal Phase; Magnetic Resonance Imaging; Malignant Neoplasms; Measures; Menorrhagia; Menstrual cycle; Mifepristone; Oral Contraceptives; Outcome; Participant; Pharmaceutical Preparations; Phase; Premenopause; Prevention; Preventive service; Procedures; Progesterone; Progesterone Receptors; Progestins; Questionnaires; Randomized; Risk; Tamoxifen; Thromboembolism; Time; United States; Uterine Fibroids; Venous; Woman; aged; base; cancer risk; comparison group; emergency contraception; experience; high risk; malignant breast neoplasm; novel therapeutics; prevent; primary outcome; prospective; public health relevance; reproductive

 DESCRIPTION (provided by applicant): Breast cancer accounts for almost a quarter of all cancers in women. It is estimated that in the U.S. in 2014 more than 230,000 women were diagnosed with the disease and 40,000 died of the disease. Tamoxifen is an effective chemopreventive agent; however, it is not widely used, in part due to its increased risks of endometrial cancer and venous thromboembolism. The United States Preventive Services Task Force recommends tamoxifen use only for those at high risk of breast cancer. There is an urgent need to develop acceptable means of preventing the disease both for high risk and average risk women. The proposed study is a clinical trial in premenopausal women aged 18-40 to evaluate the capacity of daily Ulipristal Acetate (UPA) to reduce breast epithelial cell proliferation and to measure its effect compared to that found with a combined estrogen-progestin oral contraceptive (COC). UPA is a selective progesterone receptor modulator (SPRM) in use as daily medication up to 12 months for the treatment of menorrhagia due to uterine fibroids, and is currently in trials in the U.S. to evaluate its use as a daily contraceptie. The proposed study will allow us to investigate the potential of UPA to reduce breast cell proliferation and possibly breast cancer risk if used over an extended period of time. We will compare breast cell proliferation, as measured by Ki67 expression in breast biopsies, at the end of 3 months treatment to baseline values in the 2 groups (UPA and COC). We will also compare the changes in the 2 groups to each other. The comparison of the effect of UPA to that of a conventional COC is because of UPA's potential use as a daily contraceptive. Cell proliferation in the breast occurs throughout the menstrual cycle and is roughly twice as high in the luteal phase (elevated progesterone phase) of the cycle. The actions of hormones on the breast are rapid and an anti-progestin such as UPA, which will block the action of progesterone in the breast would be predicted to quickly lower breast cell proliferation in premenopausal women. Effects of UPA on the endometrium continue to be studied and are reassuring. COC use has not been found to lower breast cell proliferation and is not associated with any decrease in risk of breast cancer. The changes in breast cell proliferation will also be compared to changes seen on breast MRI. If these are highly correlated future studies will be able to be done without the need for breast biopsies.