A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen.
Level 2 - randomized trial
Randomized, double-blind, placebo-controlled trial
PubMed 28560655 · doi:10.1007/s10549-017-4292-7
What was done
In a double-blind, randomized, placebo-controlled trial, 130 women taking tamoxifen were assigned to receive either oral BioResponse DIM (BR-DIM, 150 mg twice daily) or placebo for 12 months. The primary endpoint was change in the urinary 2/16α-hydroxyestrone (2/16α-OHE1) ratio. Secondary measures included urinary 4-hydroxyestrone, serum estrogens, sex hormone-binding globulin (SHBG), breast density by mammography or MRI, tamoxifen metabolite levels, and safety.
What was found
Of 130 enrolled women, 98 completed the 12-month intervention (51 placebo, 47 BR-DIM; compliance >91%). BR-DIM significantly increased the urinary 2/16α-OHE1 ratio compared to placebo (+3.2 [0.8, 8.4] vs -0.7 [-1.7, 0.8], P < 0.001) and raised serum SHBG (+25 ± 22 nmol/L vs +1.1 ± 19 nmol/L). No differences were observed in breast density. However, BR-DIM significantly reduced plasma concentrations of tamoxifen metabolites, including endoxifen, 4-hydroxytamoxifen, and N-desmethyl-tamoxifen (P < 0.001). Adverse events were minimal and similar between groups.
Why it matters
While BR-DIM favorably alters estrogen metabolism and elevates SHBG, it substantially decreases circulating levels of key active tamoxifen metabolites like endoxifen, raising concern that co-supplementation could potentially reduce tamoxifen efficacy.
Limits
The study evaluated surrogate biomarkers rather than long-term clinical outcomes such as breast cancer recurrence or survival. Drop-out reduced the final analysis set from 130 to 98 participants, and specific mechanism-driven thresholds for clinical impairment of tamoxifen activity were not established.
Cited by
- supports Diindolylmethane (DIM) can inhibit or lower estrogen levels.