Department of Obstetrics and Gynecology, Columbia University Irving Medical Center, PH 16-69, 630 West 168th Street, New York, NY, 10032, USA.
Department of Pathology, Columbia University Irving Medical Center, New York, NY, USA.
Breast Cancer Res Treat. 2022 Apr;192(2):321-329. doi: 10.1007/s10549-021-06503-1. Epub 2022 Jan 11.
The proliferation of breast epithelial cells increases during the luteal phase of the menstrual cycle, when they are exposed to progesterone, suggesting that ulipristal acetate, a selective progestin-receptor modulator (SPRM), may reduce breast cell proliferation with potential use in breast cancer chemoprevention.
Women aged 18-39 were randomized 1:1 to ulipristal 10-mg daily or to a combination oral contraceptive (COC) for 84 days. Participants underwent a breast biopsy and breast MRI at baseline and at end of study treatment. Proliferation of breast TDLU cells was evaluated by Ki67 immunohistochemical stain. We evaluated the breast MRIs for background parenchymal enhancement (BPE). All slides and images were masked for outcome evaluation.
Twenty-eight treatment-compliant participants completed the study; 25 of whom had evaluable Ki67 results at baseline and on-treatment. From baseline to end of treatment, Ki67 % positivity (Ki67%+) decreased a median of 84% in the ulipristal group (N = 13; 2-sided p (2p) = 0.040) versus a median increase of 8% in the COC group (N = 12; 2p = 0.85). Median BPE scores decreased from 3 to 1 in the ulipristal group (p = 0.008) and did not decrease in the COC group.
Ulipristal was associated with a major decrease in Ki67%+ and BPE. Ulipristal would warrant further investigation for breast cancer chemoprevention were it not for concerns about its liver toxicity. Novel SPRMs without liver toxicity could provide a new approach to breast cancer chemoprevention.
NCT02922127, 4 October 2016.
在黄体期，当乳腺上皮细胞暴露于孕激素时，其增殖增加，这表明选择性孕激素受体调节剂（SPRMs）依伴侬可能通过减少乳腺细胞增殖来发挥潜在的乳腺癌化学预防作用。
18-39 岁的女性患者被随机 1:1 分配至依伴侬 10mg/天组或复方口服避孕药（COC）组，接受为期 84 天的治疗。所有患者在基线和研究治疗结束时均进行了乳腺活检和乳腺 MRI 检查。通过 Ki67 免疫组化染色评估乳腺 TDLU 细胞的增殖情况。我们评估了乳腺 MRI 的背景实质强化（BPE）情况。所有切片和图像均进行了结果评估盲法处理。
28 名依从性良好的参与者完成了研究；其中 25 名在基线和治疗期间有可评估的 Ki67 结果。与 COC 组相比（N=12），依伴侬组的 Ki67%阳性（Ki67%+）从基线到治疗结束中位数降低了 84%（N=13；双侧 p（2p）=0.040），而 COC 组中位数增加了 8%（2p=0.85）。依伴侬组的 BPE 评分从 3 分降至 1 分（p=0.008），而 COC 组的 BPE 评分没有下降。
依伴侬与 Ki67%+和 BPE 的显著降低有关。如果不是因为担心其肝毒性，依伴侬可能会进一步被研究用于乳腺癌化学预防。没有肝毒性的新型 SPRMs 可能为乳腺癌化学预防提供一种新方法。
NCT02922127，2016 年 10 月 4 日。
