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

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.

[1]  L. V. van't Veer,et al.  Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. , 2007, The American journal of clinical nutrition.

[2]  J. Levy,et al.  Tomato lycopene extract supplementation decreases insulin-like growth factor-I levels in colon cancer patients , 2007, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[3]  J. Woodside,et al.  Effect of lycopene supplementation on insulin-like growth factor-1 and insulin-like growth factor binding protein-3: a double-blind, placebo-controlled trial , 2007, European Journal of Clinical Nutrition.

[4]  L. V. van't Veer,et al.  Isolated isoflavones do not affect the circulating insulin-like growth factor system in men at increased colorectal cancer risk. , 2007, The Journal of nutrition.

[5]  W. Koff,et al.  Effect of the consumption of tomato paste on plasma prostate-specific antigen levels in patients with benign prostate hyperplasia. , 2006, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[6]  X. Coumoul,et al.  Absence of the full-length breast cancer-associated gene-1 leads to increased expression of insulin-like growth factor signaling axis members. , 2006, Cancer research.

[7]  P. Riso,et al.  Effect of a Tomato Drink Intervention on Insulin-Like Growth Factor (IGF)-1 Serum Levels in Healthy Subjects , 2006, Nutrition and cancer.

[8]  H. Werner,et al.  Transcriptional regulation of the insulin-like growth factor-I receptor gene in breast cancer , 2006, Molecular and Cellular Endocrinology.

[9]  F. Berrino,et al.  IGF-I, IGFBP-3 and breast cancer in young women: a pooled re-analysis of three prospective studies , 2005, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[10]  J. Buring,et al.  Dietary and Plasma Lycopene and the Risk of Breast Cancer , 2005, Cancer Epidemiology Biomarkers & Prevention.

[11]  A. Roddam,et al.  A prospective study of serum insulin-like growth factor-I (IGF-I), IGF-II, IGF-binding protein-3 and breast cancer risk , 2005, British Journal of Cancer.

[12]  S. Hankinson,et al.  Circulating Levels of Insulin-like Growth Factors, their Binding Proteins, and Breast Cancer Risk , 2005, Cancer Epidemiology Biomarkers & Prevention.

[13]  K. Wertz,et al.  Lycopene reduced gene expression of steroid targets and inflammatory markers in normal rat prostate , 2005, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[14]  W. Willett,et al.  Plasma carotenoids, retinol, and tocopherols and risk of breast cancer. , 2005, American journal of epidemiology.

[15]  L. V. van't Veer,et al.  The insulin-like growth factor system in cancer prevention: potential of dietary intervention strategies. , 2005, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[16]  N. Gupta,et al.  Lycopene: a novel drug therapy in hormone refractory metastatic prostate cancer. , 2004, Urologic oncology.

[17]  S. Hankinson,et al.  Insulin-like growth factors and neoplasia , 2004, Nature Reviews Cancer.

[18]  K. Wertz,et al.  Lycopene and Vitamin E interfere with autocrine/paracrine loops in the Dunning prostate cancer model , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[19]  Matthias Egger,et al.  Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis , 2004, The Lancet.

[20]  D. Voskuil,et al.  Insulin-Like Growth Factor (IGF)-System mRNA Quantities in Normal and Tumor Breast Tissue of Women with Sporadic and Familial Breast Cancer Risk , 2004, Breast Cancer Research and Treatment.

[21]  C. Swanson,et al.  Relationships of serum carotenoids, retinol, α-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States) , 2004, Cancer Causes & Control.

[22]  W. Saris,et al.  Reproducibility and relative validity of the short questionnaire to assess health-enhancing physical activity. , 2003, Journal of clinical epidemiology.

[23]  J. Levy,et al.  Lycopene in serum, skin and adipose tissues after tomato-oleoresin supplementation in patients undergoing haemorrhoidectomy or peri-anal fistulotomy , 2003, British Journal of Nutrition.

[24]  L. Hennighausen,et al.  Reduced circulating insulin-like growth factor I levels delay the onset of chemically and genetically induced mammary tumors. , 2003, Cancer research.

[25]  R. Russell,et al.  Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. , 2003, Cancer research.

[26]  R. Krajcik,et al.  Insulin-like growth factor I (IGF-I), IGF-binding proteins, and breast cancer. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[27]  P. Bowen,et al.  Tomato Sauce Supplementation and Prostate Cancer: Lycopene Accumulation and Modulation of Biomarkers of Carcinogenesis , 2002, Experimental biology and medicine.

[28]  F. Berrino,et al.  Fasting glucose is a risk factor for breast cancer: a prospective study. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[29]  X. Shu,et al.  Insulin-like growth factors and breast cancer risk in Chinese women. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[30]  A. Alberg,et al.  Prospective study of carotenoids, tocopherols, and retinoid concentrations and the risk of breast cancer. , 2002, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[31]  F. Granado,et al.  A European multicentre, placebo-controlled supplementation study with alpha-tocopherol, carotene-rich palm oil, lutein or lycopene: analysis of serum responses. , 2002, Clinical science.

[32]  G. Siest,et al.  An isocratic liquid chromatographic method with diode-array detection for the simultaneous determination of alpha-tocopherol, retinol, and five carotenoids in human serum. , 2002, Journal of chromatographic science.

[33]  E. Riboli,et al.  A cross-sectional study of IGF-I determinants in women , 2001, European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation.

[34]  M. Banerjee,et al.  Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. , 2001, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[35]  R. Shore,et al.  Serum insulin‐like growth factor‐I and breast cancer , 2000, International journal of cancer.

[36]  M. Karas,et al.  Lycopene Interferes With Cell Cycle Progression and Insulin-Like Growth Factor I Signaling in Mammary Cancer Cells , 2000, Nutrition and cancer.

[37]  D. Leroith,et al.  Normal growth and development in the absence of hepatic insulin-like growth factor I. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  S. Ahn,et al.  Correlation between carotenoid concentrations in serum and normal breast adipose tissue of women with benign breast tumor or breast cancer. , 1998, The Journal of nutrition.

[39]  David J Hunter,et al.  Circulating concentrations of insulin-like growth factor I and risk of breast cancer , 1998, The Lancet.

[40]  A. Rao,et al.  Bioavailability and in vivo antioxidant properties of lycopene from tomato products and their possible role in the prevention of cancer. , 1998, Nutrition and cancer.

[41]  J. French,et al.  Dietary restriction reduces insulin-like growth factor I levels, which modulates apoptosis, cell proliferation, and tumor progression in p53-deficient mice. , 1997, Cancer research.

[42]  W. Willett,et al.  Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. , 1997, The American journal of clinical nutrition.

[43]  T. C. Linders,et al.  Insulin‐like growth‐factor‐binding protein 3 is decreased in early‐stage operable pre‐menopausal breast cancer , 1995, International journal of cancer.

[44]  M. Danilenko,et al.  Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. , 1995, Nutrition and cancer.