Selection of surrogate endpoint biomarkers (SEBs) and appropriate study design are two of the main challenges in evaluating potential chemopreventive agents. In a prospective random fine-needle aspiration (FNA) study of women at high risk of development of breast cancer, we previously demonstrated t
Chemoprevention of breast cancer: The Italian experience
โ Scribed by Andrea Decensi; Bernardo Bonanni; Aliana Guerrieri-Gonzaga; Rosalba Torrisi; Lapo Manetti; Chris Robertson; Giuseppe De Palo; Franca Formelli; Alberto Costa; Umberto Veronesi
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 142 KB
- Volume
- 77
- Category
- Article
- ISSN
- 0730-2312
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โฆ Synopsis
The activity of our group is focused on the conduction of chemoprevention clinical trials of breast cancer in at-risk subjects, among which we include women on hormone replacement therapy (HRT). The role of the insulin-like growth factor (IGF) system and of mammographic breast density as surrogate biomarkers for breast cancer prevention is also being investigated. The IGF system is involved in human carcinogenesis of several solid tumors. IGF-I is a potent mitogen for breast cancer cells; elevated circulating IGF-I levels have been associated with a higher risk of premenopausal breast cancer, prostate and colorectal cancer in prospective studies. Both tamoxifen and the synthetic retinoid fenretinide (4-HPR) have been shown to decrease plasma IGF-I levels. A trial of their combination is ongoing in premenopausal women with increased risk for breast cancer. Mammographic breast density has also been associated with an increased risk of breast cancer in several prospective studies. In this article, we discuss the rationale for selection of appropriate cohorts, candidate agents, and putative surrogate biomarkers in our breast cancer prevention trials. Moreover, updated results of the secondary prevention trial of 4-HPR and of the primary prevention trial of tamoxifen are presented. Finally, the rationale for a reduction of tamoxifen dose in future prevention trials is provided.
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