DIETARY RETINOIDS AND CAROTENOIDS IN RODENT MODELS OF MAMMARY TUMORIGENESIS

In this review of the scientific literature the relationship between r etinoids, carotenoids, and mammary carcinogenesis is examined. Several retinoids have shown promise as chemopreventive agents against chemic ally induced mammary carcinogenesis in mice and especially in rats. Th e most promising retinoids are retinyl acetate (RA) and N-(4-hydroxyph enyl)retinamide (4-HPR, fenretinide). In rats, dietary administration of these retinoids reduced tumor incidence and multiplicity, and incre ased the latency of DMBA or MNU-induced mammary cancers. In mice, LC-H PR reduced the number of hyperplastic alveolar nodules and the number of tumors in MTV-and MTV+ mice, respectively. Among retinoids, 4-HPR i s at present the most promising analogue, due to its ability to concen trate in the mammary gland. The combination of 4-HPR with tamoxifen no t only is more effective in suppressing breast cancer than either agen t alone, but also inhibits the appearance of subsequent cancers follow ing the surgical removal of the first tumor. These studies suggest tha t retinoids, like tamoxifen, may be applicable to the prevention of co ntralateral breast cancer in women who underwent breast cancer surgery . It is also becoming evident that differentiation therapy and chemopr evention can become attractive alternative approaches to intensive cyt otoxic chemotherapy. The role of carotenoids in the prevention of mamm ary carcinogenesis, however, is ambiguous. Poor absorption and low lev els of carotenoids that reach the target tissues complicate interpreta tion of data in rodent models of mammary carcinogenesis. Very few anim al studies are presently available in which purified carotenoids were found effective against mammary carcinogenesis. These results do not j ustify undertaking clinical evaluation of individual carotenoids again st breast cancer at this time.