Dietary retinoids and carotenoids in rodent models of mammary tumorigenesis

In this review of the scientific literature the relationship between retinoids, carotenoids, and mammary carcinogenesis is examined. Several retinoids have shown promise as chemopreventive agents against chemically induced mammary carcinogenesis in mice and especially in rats. The most promising retinoids are retinyl acetate (RA) and N-(4-hydroxyphenyl)retinamide (4-HPR, fenretinide). In rats, dietary administration of these retinoids reduced tumor incidence and multiplicity, and increased the latency of DMBA or MNU-induced mammary cancers. In mice, LC-HPR reduced the number of hyperplastic alveolar nodules and the number of tumors in MTV-and MTV+ mice, respectively. Among retinoids, 4-HPR is at present the most promising analogue, due to its ability to concentrate in the mammary gland. The combination of 4-HPR with tamoxifen not only is more effective in suppressing breast cancer than either agent alone, but also inhibits the appearance of subsequent cancers following the surgical removal of the first tumor. These studies suggest that retinoids, like tamoxifen, may be applicable to the prevention of contralateral breast cancer in women who underwent breast cancer surgery. It is also becoming evident that differentiation therapy and chemoprevention can become attractive alternative approaches to intensive cytotoxic chemotherapy. The role of carotenoids in the prevention of mammary carcinogenesis, however, is ambiguous. Poor absorption and low levels of carotenoids that reach the target tissues complicate interpretation of data in rodent models of mammary carcinogenesis. Very few animal studies are presently available in which purified carotenoids were found effective against mammary carcinogenesis. These results do not justify undertaking clinical evaluation of individual carotenoids against breast cancer at this time.