Chemoprevention of breast cancer: The Italian experience

The activity of our group is focused on the conduction of chemoprevention c linical trials of breast cancer in at-risk subjects, among which we include women on hormone replacement therapy (HRT). The role of the insulin-like g rowth factor (IGF) system and of mammographic breast density as surrogate b iomarkers for breast cancer prevention is also being investigated. The IGF system is involved in human carcinogenesis of several solid tumors. IGF-I i s a potent mitogen for breast cancer cells; elevated circulating IGF-I leve ls have been associated with a higher risk of premenopausal breast cancer, prostate and colorectal cancer in prospective studies. Both tamoxifen and t he synthetic retinoid fenretinide (4-HPR) have been shown to decrease plasm a IGF-1 levels. A trial of their combination is ongoing in premenopausal wo men with increased risk for breast cancer. Mammographic breast density has also been associated with an increased risk of breast cancer in several pro spective studies. In this article, we discuss the rationale for selection o f appropriate cohorts, candidate agents, and putative surrogate biomarkers in our breast cancer prevention trials. Moreover, updated results of the se condary prevention trial of 4-HPR and of the primary prevention trial of ta moxifen are presented. Finally, the rationale for a reduction of tamoxifen dose in future prevention trials is provided. J. Cell. Biochem. Suppl. 34:8 4-96, 2000. (C) 2000 Wiley-Liss. Inc.