Sulforaphane Bioavailability and Chemopreventive Activity in Women Scheduled for Breast Biopsy

Cancer Prev Res (Phila). 2015 Dec;8(12):1184-1191. doi: 10.1158/1940-6207.CAPR-15-0119. Epub 2015 Oct 28.

Abstract

Epidemiologic studies suggest a protective effect of cruciferous vegetables on breast cancer. Sulforaphane (SFN), an active food component derived from crucifers, has been shown to be effective in breast cancer chemoprevention. This study evaluated the chemopreventive effect of SFN on selective biomarkers from blood and breast tissues. In a 2- to 8-week double-blinded, randomized controlled trial, 54 women with abnormal mammograms and scheduled for breast biopsy were randomized to consume a placebo or a glucoraphanin (GFN) supplement providing SFN (n = 27). Plasma and urinary SFN metabolites, peripheral blood mononuclear cell (PBMC) histone deacetylase (HDAC) activity, and tissue biomarkers (H3K18ac, H3K9ac, HDAC3, HDAC6, Ki-67, p21) were measured before and after the intervention in benign, ductal carcinoma in situ, or invasive ductal carcinoma breast tissues. Within the supplement group, Ki-67 (P = 0.003) and HDAC3 (P = 0.044) levels significantly decreased in benign tissue. Pre-to-postintervention changes in these biomarkers were not significantly different between treatment groups after multiple comparison adjustment. GFN supplementation was associated with a significant decrease in PBMC HDAC activity (P = 0.04). No significant associations were observed between SFN and examined tissue biomarkers when comparing treatment groups. This study provides evidence that GFN supplementation for a few weeks is safe but may not be sufficient for producing changes in breast tissue tumor biomarkers. Future studies employing larger sample sizes should evaluate alternative dosing and duration regimens to inform dietary SFN strategies in breast cancer chemoprevention.

Trial registration: ClinicalTrials.gov NCT00843167.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Anticarcinogenic Agents / pharmacokinetics
  • Anticarcinogenic Agents / therapeutic use*
  • Biological Availability
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / prevention & control*
  • Carcinoma, Intraductal, Noninfiltrating / prevention & control*
  • Chemoprevention / methods
  • Dietary Supplements
  • Double-Blind Method
  • Female
  • Humans
  • Immunohistochemistry
  • Isothiocyanates / pharmacokinetics
  • Isothiocyanates / therapeutic use*
  • Mass Spectrometry
  • Sulfoxides

Substances

  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • Isothiocyanates
  • Sulfoxides
  • sulforaphane

Associated data

  • ClinicalTrials.gov/NCT00843167