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.

 描述（由申请人提供）：乳腺癌占女性所有癌症的近四分之一。据估计，2014年美国有超过23万名妇女被诊断患有这种疾病，4万人死于这种疾病。他莫昔芬是一种有效的化学预防剂;然而，它并没有被广泛使用，部分原因是它增加了子宫内膜癌和静脉血栓栓塞的风险。美国预防服务工作组建议他莫昔芬仅用于乳腺癌高危人群。迫切需要为高风险和一般风险妇女制定可接受的预防疾病的方法。 这项拟议的研究是一项在18-40岁绝经前妇女中进行的临床试验，旨在评估每日醋酸乌利司他（UPA）减少乳腺上皮细胞增殖的能力，并测量其与雌激素-孕酮联合口服避孕药（COC）相比的效果。UPA是一种选择性孕酮受体调节剂（SPRM），作为每日药物使用长达12个月，用于治疗子宫肌瘤引起的月经过多，目前正在美国进行试验，以评估其作为每日避孕药的用途。这项拟议的研究将使我们能够调查UPA在减少乳腺细胞增殖和可能的乳腺癌风险方面的潜力，如果长期使用的话。 我们将比较两组（UPA和COC）在3个月治疗结束时的乳腺细胞增殖（通过乳腺活检组织中Ki 67表达测量）与基线值。我们还将比较两组的变化。UPA与传统COC的效果比较是因为UPA作为日常避孕药的潜在用途。 乳腺中的细胞增殖发生在整个月经周期中，并且在周期的黄体期（升高的孕酮期）大约是两倍。激素对乳房的作用是迅速的，并且将阻断孕酮在乳房中的作用的抗孕酮蛋白如UPA将被预测为快速降低绝经前妇女的乳腺细胞增殖。UPA对子宫内膜的影响仍在研究中，并令人放心。COC的使用没有发现降低乳腺细胞增殖，也与乳腺癌风险的任何降低无关。 乳腺细胞增殖的变化也将与乳腺MRI上观察到的变化进行比较。如果这些是高度相关的，未来的研究将能够在不需要乳腺活检的情况下进行。