A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen

• DOI: 10.1007/s10549-017-4292-7
• Publication Date: 2017-05-30T09:06:28Z
• Authors: Cynthia A. Thomson; H. H. Sherry Chow; Betsy C. Wertheim; Denise J. Roe; Alison Stopeck; Gertraud Maskarinec; Maria Altbach; Pavani Chalasani; Chuan Huang; Meghan B. Strom; Jean-Philippe Galons; Patricia A. Thompson
• Keywords: Adult; Hydroxyestrones; Indoles; Time Factors; Breast Neoplasms; Middle Aged; 3. Good health; Tamoxifen; 03 medical and health sciences; Treatment Outcome; 0302 clinical medicine; Double-Blind Method; Sex Hormone-Binding Globulin; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Humans; Female; Mammography

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.