THE COMBINED EFFECTS OF DIETARY-FAT AND ESTROGEN ON SURVIVAL, 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED BREAST-CANCER AND PROLACTIN METABOLISM IN RATS

The relationships between dietary fat concentration (10 or 40% of energy), fat source (corn oil or beef tallow) and estrogen (control, ovariectomy or ovariectomy with estrogen replacement) to 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast carcinogenesis and survival in rats were studied in a 2 x 2 x 3 factorial experiment. Female Sprague-Dawley rats given DMBA (2.5 mg/100 g body wt, intragastric) at 55 d of age were randomly allocated to three groups 48 h later: sham ovariectomy (control), ovariectomy (OVX) or ovariectomy with a subcutaneous estrogen implant (OVX+E). Each group was subdivided into dietary groups fed 10 and 40% of energy as corn oil or beef tallow for 70 wk. OVX+E rats exhibited serum estrogen concentrations in excess of physiologic values. Survival at 70 wk for the 3 hormonal groups was control 51%, OVX 67% and OVX+E 13%. Mortality in controls was doubled by feeding a high fat diet; no diet effect was detected in OVX or OVX+E rats. Palpable tumors developed in 74, 14 and 60% of control, OVX and OVX+E rats, respectively. High fat diets approximately doubled the hazard of developing a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in control, OVX and OVX+E rats, respectively. The odds of having any tumor, an adenocarcinoma or an adenoma were multiplied by 3.6, 2.8 and 2.3, respectively, for rats fed high vs. low fat. Additional studies showed that diet had no effect on serum prolactin or estrogen concentrations or metabolism and clearance of intravenously administered radiolabeled prolactin. We demonstrated that high dietary fat concentration enhances breast carcinogenesis independently of cyclic ovarian function, although the presence of estrogen may be a prerequisite for significant dietary modulation. The effect of fat on breast cancer is not mediated by major changes in systemic prolactin metabolism.