The role of a high-fat diet in enhancing the development of mammary tumors in ovariectomized rats.

The incidences of mammary tumors in female Sprague-Dawley rats injected with 7,12-dimethylbenz-(a)anthracene (DMBA) on day 50, ovariectomized 80 days later, and then maintained for 40 weeks on semipurified high-fat (20%) and low-fat (0.5%) high-fat diets, were 57% and 25%, respectively. In addition, the group exhibited significantly higher tumor multiplicities than the low-fat group (0.78 vs 0.25 tumors/total rats at risk). The weight gains of the HF and LF groups were similar, indicating that the differences in tumor yields were due to the fat content of the diet per se and not to caloric insufficiency or obesity. These results indicate that a high-fat diet has a tumor-enhancing effect in the absence of normal periodic ovarian secretions. Extragonadal estrogen production stimulated by high dietary fat intake may play a role, possibly by inducing secretion of the tumor-promoting hormone prolactin. The etiological, preventive, and therapeutic implications of these results with regard to human breast cancer are discussed.