Sexual maturation, mammary gland differentiation and breast cancer risk are differentially effected by whole foods compared to preformed vitamin A in the SD rat

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The years between puberty and first childbirth have been identified as the most crucial in establishing breast cancer risk. Therefore, arguments have been made for shifting the focus of breast cancer prevention strategies to youth. Epidemiological data demonstrate an inverse relationship between adult vitamin A intake and breast cancer risk. Because breast development occurs primarily during adolescence, we propose that adolescence represents an optimal window for vitamin A-based dietary interventions. We investigated effects of physiologic levels of preformed vitamin A on mammary development and breast cancer risk in the SD rat, by feeding experimental diets from 21-63 days. We found an inverse relationship between adolescent vitamin A intake and mammary development, with mild deficiency enhancing and mild supplementation (7X RDA) suppressing alveolar differentiation. Protection from MNU-induced carcinogenesis was observed only in the vitamin A adequate group, with vitamin A levels above and below adequate levels associating with tumor promotion. We conclude that 1) vitamin A is a powerful modulator of hormone signaling during the critical window of adolescent mammary gland development, and 2) vitamin A intake, restricted to adolescence, influences life-long breast cancer risk. We suggest that the beneficial effects of vitamin A may require additional dietary components that are absent from AIN 93 G. To address this question we developed whole food based diets, matched in I.U. of vitamin A, to the diets described above. Animals fed the fruits and vegetable-based vitamin A enriched diet between 21- 63 days of age had significantly delayed sexual maturation and inhibition of mammary maturation. This fruits and vegetable-based diet also inhibited mammary tumorigenesis, thus providing a protective effect as predicted from epidemiological studies. These observations may have significant relevance, as early onset of menarche, and hormones that stimulate alveogenesis, are independent risk factors for breast cancer. Our study suggests that maximum protection against breast cancer results from ingestion of carotenoid-rich foods in a whole foods diet. Work supported by the U.S. Army Medical Research and Materiel Command and by the American Institute of Cancer Research.