Sk. Clinton et al., THE COMBINED EFFECTS OF DIETARY-FAT AND ESTROGEN ON SURVIVAL, 7,12-DIMETHYLBENZ(A)ANTHRACENE-INDUCED BREAST-CANCER AND PROLACTIN METABOLISMIN RATS, The Journal of nutrition, 125(5), 1995, pp. 1192-1204
The relationships between dietary fat concentration (10 or 40% of ener
gy), fat source (corn oil or beef tallow) and estrogen (control, ovari
ectomy 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-Dawl
ey 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 estrog
en 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 value
s. 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 f
at diet; no diet effect was detected in OVX or OVX+E rats. Palpable tu
mors developed in 74, 14 and 60% of control, OVX and OVX+E rats, respe
ctively. High fat diets approximately doubled the hazard of developing
a palpable tumor. Adenocarcinoma prevalence was 58, 12 and 63% in con
trol, 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, r
espectively, 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 enhanc
es breast carcinogenesis independently of cyclic ovarian function, alt
hough the presence of estrogen may be a prerequisite for significant d
ietary modulation. The effect of fat on breast cancer is not mediated
by major changes in systemic prolactin metabolism.