The present study investigated the problem of whether or not the intake of an Western-style diet will induce within the host a specified hormonal change that increases the risk for breast cancer (BC). The key observations obtained are as follows: 1) The risk for BC in Japan has been increasing for the last 20 years in parallel with the Westernization of dietary habits (increase of fat and animal protein in the diet). 2) A Japanese BC patient is distinguishable from a corresponding normal control by (a) an increase of waist/hip ratio (more specifically, an increase of abdominal fat) and (b) a decrease in the number of live births (relative infertility). Height, weight and height-adjusted weight all cannot distinguish the former from the latter. 3) The former is also distinguishable from the latter by dual steroidal disorders of ovarian dysfunction (progesterone depression) and hypercorticoidism, as revealed by a case control comparison of urinary steroid excretions. 4) The long-term maintenance of an experimental mouse on a fat-rich diet increased abdominal fat weight at an adult age, but not at a young age. 5) In the same experiment, the fat-rich diet produced a reduction of plasma progesterone at an early stage, and also produced dual changes of progesterone depression and corticosterone stimulation at a late stage of experiment. Plasma estradiol was little affected by an excess of dietary fat. 6) In an adult mouse, the weight of abdominal fat was increased by corticosterone treatment and was decreased by estradiol treatment. The suppressive effect of estradiol on abdominal fat weight was dose-dependent. In conclusion, our findings seem to suggest the possibility that a fat rich diet may produce dual steroidal disorders of ovarian dysfunction and hypercorticoidism which in turn will open the way to breast carcinogenesis by activating 2 proto-oncogens at the initiation and promotion steps.

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