Steroid hormones and human breast cancer. An hypothesis

The likely occurrence of two distinct types of human breast cancer is discussed. In the development of the "Western-environmental" or "adrenal" type, it is proposed that dehydroepiandrosterone sulphate (DHEAS), secreted by the adrenal, may be implicated. This steroid is metabolized by mammary tumors to active androgens and estrogens. That these metabolic pathways are very similar to that in skin is emphasized and this is possibly explained by evolution of the mammary gland from primitive sweat glands. Formation of DHEAS from DHEA in mammary tumors, claimed to be correlated with an individual subject's prognosis and response to hormone ablation, is discussed in the light of a possible regulatory role of the sulphotransferase. It is proposed furthermore that a specific control of DHEAS secretion in the adrenal may exist at the level of the sulphurylation step. Nutritional factors are also possibly implicated here and these are discussed in the light of: 1) a possible higher secretion rate of DHEAS in obese subjects; and 2) the low breast cancer incidence in the Japanese and the accompanying low blood DHEAS levels.