DOSE-RANGING STUDY OF INDOLE-3-CARBINOL FOR BREAST-CANCER PREVENTION

Sixty women at increased risk for breast cancer were enrolled in a pla cebo-controlled, double-blind dose-ranging chemoprevention study of in dole-3-carbinol (13C). Fifty-seven of these women with a mean age of 4 7 years (range 22-74) completed the study. Each woman took a placebo c apsule or an 13C capsule daily for a total of 4 weeks; none of the wom en experienced any significant toxicity effects. The urinary estrogen metabolite ratio of 2-hydroxyestrone to 16 alpha-hydroxyestrone, as de termined by an ELISA assay, served as the surrogate endpoint biomarker (SEB). Perturbation in the levels of SEE from baseline was comparable among women in the control (C) group and the 50, 100, and 200 mg low- dose (LD) group. Similarly, it was comparable among women in the 300 a nd 400 mg high-dose (HD) group. Regression analysis showed that peak r elative change of SEE for women in the HD group was significantly grea ter than that for women in the C and LD groups by an amount that was i nversely related to baseline ratio; the difference at the median basel ine ratio was 0.48 with 95% confidence interval (0.30, 0.67). No other factors, such as age and menopausal status, were found to be signific ant in the regression analysis. The results in this study suggest that 13C at a minimum effective dose schedule of 300 mg per day is a promi sing chemopreventive agent for breast cancer prevention. A larger stud y to validate these results and to identify an optimal effective dose schedule of 13C for long-term breast cancer chemoprevention will be ne cessary. (C) 1998 Wiley-Liss, Inc.