Thomson Cynthia A, Chow H H Sherry, Wertheim Betsy C, Roe Denise J, Stopeck Alison, Maskarinec Gertraud, Altbach Maria, Chalasani Pavani, Huang Chuan, Strom Meghan B, Galons Jean-Philippe, Thompson Patricia A
Department of Health Promotion Sciences, Mel and Enid Zuckerman College of Public Health, University of Arizona, 3950 S. Country Club, Suite 3210, Tucson, AZ, 85714, USA.
University of Arizona Cancer Center, Tucson, AZ, USA.
Breast Cancer Res Treat. 2017 Aug;165(1):97-107. doi: 10.1007/s10549-017-4292-7. Epub 2017 May 30.
Diindolylmethane (DIM), a bioactive metabolite of indole-3-carbinol found in cruciferous vegetables, has proposed cancer chemoprevention activity in the breast. There is limited evidence of clinically relevant activity of DIM or long-term safety data of its regular use. A randomized, double-blind, placebo-controlled trial was conducted to determine the activity and safety of combined use of BioResponse DIM® (BR-DIM) with tamoxifen.
Women prescribed tamoxifen (n = 130) were randomly assigned oral BR-DIM at 150 mg twice daily or placebo, for 12 months. The primary study endpoint was change in urinary 2/16α-hydroxyestrone (2/16α-OHE1) ratio. Changes in 4-hydroxyestrone (4-OHE1), serum estrogens, sex hormone-binding globulin (SHBG), breast density, and tamoxifen metabolites were assessed.
Ninety-eight women (51 placebo, 47 DIM) completed intervention; compliance with treatment was >91%. BR-DIM increased the 2/16α-OHE1 ratio (+3.2 [0.8, 8.4]) compared to placebo (-0.7 [-1.7, 0.8], P < 0.001). Serum SHBG increased with BR-DIM compared to placebo (+25 ± 22 and +1.1 ± 19 nmol/L, respectively). No change in breast density measured by mammography or by MRI was observed. Plasma tamoxifen metabolites (endoxifen, 4-OH tamoxifen, and N-desmethyl-tamoxifen) were reduced in women receiving BR-DIM versus placebo (P < 0.001). Minimal adverse events were reported and did not differ by treatment arm.
In patients taking tamoxifen for breast cancer, daily BR-DIM promoted favorable changes in estrogen metabolism and circulating levels of SHBG. Further research is warranted to determine whether BR-DIM associated decreases in tamoxifen metabolites, including effects on endoxifen levels, attenuates the clinical benefit of tamoxifen.
ClinicalTrials.gov NCT01391689.
二吲哚甲烷（DIM）是十字花科蔬菜中发现的吲哚 - 3 - 甲醇的生物活性代谢产物，已被提出具有乳腺癌化学预防活性。关于DIM临床相关活性的证据有限，其长期安全性数据也不足。开展了一项随机、双盲、安慰剂对照试验，以确定BioResponse DIM®（BR - DIM）与他莫昔芬联合使用的活性和安全性。
开具他莫昔芬处方的女性（n = 130）被随机分配，分别每日口服两次150 mg的BR - DIM或安慰剂，持续12个月。主要研究终点是尿中2/16α - 羟基雌酮（2/16α - OHE1）比值的变化。评估了4 - 羟基雌酮（4 - OHE1）、血清雌激素、性激素结合球蛋白（SHBG）、乳腺密度和他莫昔芬代谢产物的变化。
98名女性（51名安慰剂组，47名DIM组）完成干预；治疗依从性>91%。与安慰剂组（-0.7 [-1.7, 0.8]）相比，BR - DIM组使2/16α - OHE1比值升高（+3.2 [0.8, 8.4]）（P < 0.001）。与安慰剂组相比，BR - DIM组血清SHBG升高（分别为+25±22和+1.1±19 nmol/L）。通过乳腺X线摄影或MRI测量的乳腺密度未观察到变化。接受BR - DIM的女性与安慰剂组相比，血浆他莫昔芬代谢产物（endoxifen、4 - OH他莫昔芬和N - 去甲基他莫昔芬）减少（P < 0.001）。报告的不良事件极少，且各治疗组间无差异。
在服用他莫昔芬治疗乳腺癌的患者中，每日服用BR - DIM可促进雌激素代谢和SHBG循环水平的有利变化。有必要进一步研究以确定BR - DIM相关的他莫昔芬代谢产物减少，包括对endoxifen水平的影响，是否会减弱他莫昔芬的临床益处。
ClinicalTrials.gov NCT01391689。
