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（由适用提供）：乳腺癌占女性所有癌症的四分之一。据估计，在2014年，在美国，有23万名妇女被诊断出患有该疾病，40,000名死于该疾病。他莫昔芬是一种有效的化学预防剂。但是，它并未被广泛使用，部分原因是它增加了子宫内膜癌和静脉血栓主义的风险。美国预防服务工作队建议他仅适用于患有乳腺癌风险高风险的人。迫切需要开发可接受的方法来预防高风险和普通风险女性。拟议的研究是一项在18-40岁的绝经前妇女中进行的临床试验，以评估每日乙酸乌吡酯（UPA）减少乳腺上皮细胞增殖的能力，并与与雌激素 - 蛋黄酱合并的口服避孕药（COC）相比，衡量其作用。 UPA是一种选择性的孕酮受体调节剂（SPRM），可用作每日药物长达12个月的药物，用于治疗子宫纤维，目前正在美国进行试验，以评估其每日避孕药的用途。拟议的研究将使我们能够研究UPA的潜力，以减少乳腺细胞增殖和可能长时间使用的乳腺癌风险。我们将在3个月的治疗结束时通过Ki67在乳房活检中的Ki67表达与两组（UPA和COC）中的基线值进行比较。我们还将将2组的更改彼此比较。 UPA与常规COC的效果的比较是由于UPA的潜在用作每日避孕药。乳房中的细胞增殖发生在整个月经周期中，大约是黄体期（升高孕激素阶段）的两倍。骑马在乳房上的作用是迅速的，是抗蛋白酶，例如UPA，这将阻止孕酮在乳房中的作用，将迅速降低绝经前女性的乳腺细胞增殖。 UPA对子宫内膜的影响继续研究并令人放心。尚未发现COC使用可以降低乳腺细胞的增殖，并且与乳腺癌风险的降低无关。乳腺细胞增殖的变化也将与乳房MRI上的变化进行比较。如果这些是高度相关的未来研究，则可以在不需要乳房活检的情况下进行。