Effects of Lycopene on the Insulin-Like Growth Factor (IGF) System in Premenopausal Breast Cancer Survivors and Women at High Familial Breast Cancer Risk

Abstract

Insulin-like growth factor-I (IGF-I) is an important growth factor associated with increased risk of premenopausal breast cancer. We conducted a randomized, placebo-controlled, double-blind, crossover trial to evaluate whether tomato-derived lycopene supplementation (30 mg/day for 2 mo) decreases serum levels of total IGF-I in premenopausal women with 1) a history of breast cancer ( n = 24) or 2) a high familial breast cancer risk ( n = 36). Also, IGF binding protein (IGFBP) increasing effects were evaluated. Lycopene supplementation did not significantly alter serum total IGF-I and other IGF system components in the 2 study populations combined. However, statistically significant discordant results were observed between the 2 study populations (i.e., P < 0.05 for total IGF-I, free IGF-I, and IGFBP-3). Total IGF-I and IGFBP-3 were increased in the breast cancer survivor population [total IGF-I = 7.0%, 95% confidence interval (CI) = –0.2 to 14.3%; IGFBP-3 = 3.3%, 95% CI = 0.7–6.0%), and free IGF-I was decreased in the family history population (–7.6%, 95% CI = –14.6 to –0.6%). This randomized controlled trial shows that 2 mo of lycopene supplementation has no effect on serum total IGF-I in the overall study population. However, lycopene effects were discordant between the 2 study populations showing beneficial effects in high-risk healthy women but not in breast cancer survivors.

ACKNOWLEDGMENTS

This study was financially supported by the Dutch Cancer Society (Grant 2001–2579). We thank LycoRed Natural Products Industries Ltd., Beer-Sheva, Israel, for providing us with Lyc-o-Mato® supplements and placebo capsules. We thank M. Heijnen, C. Kenens, and W. Koppenol for their assistance in subject recruitment and data collection; E. Siebelink for training and assistance in coding of 24-h recalls; M. Buning, O. Dalesio, O. Van Tellingen, and D. Linders for technical support; and the following physicians for help in subject recruitment: L. Boersma, S. Veltkamp, R. Boom^†, and I. Kluijt; and all subjects for their efforts and dedication.

Notes

^a 1 participant received chemotherapy 19 years previously, which had not influenced menstrual cycles.

^a Abbreviations are as follows: LP, lycopene then placebo time sequence group; PL, placebo then lycopene time sequence group.

^b Missing data (no general questionnaire available) in 2 individuals from family history population, group PL.

^a N = 60. Abbreviations are as follows: IGFBP, IGF binding protein; SHBG, sex hormone-binding globulin.

^b Absolute or relative within-persons crossover difference between the concentration after placebo and the concentration after lycopene significantly different from zero (P < 0.05). Absolute differences were tested using a paired t-test (total IGF-I, IGFBP-2, IGFBP-3, lycopene, and SHBG) or Wilcoxon signed ranks test (free IGF-I, IGFBP-1, estradiol); relative differences were tested using a 1-sample t-test (total and free IGF-I, IGFBP-2, IGFBP-3, lycopene, and SHBG) or sign test (IGFBP-1 and estradiol).

^a Abbreviations are as follows: CI, confidence interval; BP, binding protein. Tests were paired samples t-test (total IGF-I, free IGF-I, IGFBP-2, and IGFBP-3) or Wilcoxon signed ranks test (IGFBP-1) for absolute differences and 1-sample t-test (total IGF-I, free IGF-I, IGFBP-2, and IGFBP-3) or sign test (IGFBP-1) for relative differences; for IGFBP-1, the median and range of the relative difference is reported, as the relative difference is not normally distributed.

^b absolute concentrations and difference in free IGF-I and IGFBP-1, and relative difference in IGFBP-1 are not normally distributed, therefore median (and range) instead of mean and standard deviation are reported.

^c P < 0.05.