caa a22 4500 386389500 CHVBK 20180307112109.0 cr unu---uuuuu 161130s1989 xx s 000 0 eng 10.1017/S0269727000010575 doi S0269727000010575 pii (NATIONALLICENCE)cambridge-10.1017/S0269727000010575 A new approach to the prevention of breast cancer [Elektronische Daten] While the role of oestrogens in breast cancer has been recognised for over a century, until recently our understanding of the mechanism by which they act has been limited, despite zealous efforts on the part of many investigators to seek for differences in oestrogen levels or metabolism in cancer patients. Since the initiation of breast cancer occurs many years before the detection of overt disease, it seems reasonable to suggest that these earlier studies may have been carried out at the wrong stage of the disease. Using a time invariant radiometric procedure, we have established that of the three principal sites of oestrogen metabolism at C-2, C-16α, and C-17, only C-16α hydroxylation is elevated in women with breast cancer. Further studies in women at high risk for breast cancer for familial reasons showed that they have an elevated rate of 16α-hydroxylation. Parallel studies in mice with high and low rates of spontaneous mammary tumour formation show a close parallelism between the extent of 16α-hydroxylation and tumour incidence. Studies of 16α-hydroxyoestrone, the product of 16α-hydroxylation, have demonstrated that it is a unique oestrogen, capable of binding irreversibly to the oestrogen receptor and permanently activating it. Studies on the effects of diet and drugs on the extent of C-2 and C-16α hydroxylation have shown that while the former reaction is easily increased or decreased, the latter is refractory to treatment and behaves like a constitutive enzyme. Thus, treatment with cimetidine, obesity, or high fat diets decrease the extent of C-2 hydroxylation, while high protein diets, hyperthyroidism, smoking, or dioxins increase C-2 hydroxylation. In contrast, 16α-hydroxylation is essentially unchanged in any of these conditions. A link between increased C-2 hydroxylation and decreased levels of breast and endometrial cancer is suggested by epidemiological studies in smokers. Conversely, decreases in this reaction as in obesity are associated with increased risk for these tumours. The aim of these studies is to develop a safe prophylactic regimen which will increase C-2 hydroxylation, resulting in a decrease in active oestrogen and a lower tumour incidence. Copyright © Royal Society of Edinburgh 1989 The Involvement of Oestrogen in the Development and Progression of Breast Disease nationallicence Bradlow H. Leon The Rockefeller University, 1230 York Avenue, New York, NY10021, U.S.A. Michnovicz Jon J. The Rockefeller University, 1230 York Avenue, New York, NY10021, U.S.A. Proceedings of the Royal Society of Edinburgh. Section B. Biological Sciences Royal Society of Edinburgh Scotland Foundation 95(1989), 77-86 0269-7270 95<77 1989 95 PRB https://doi.org/10.1017/S0269727000010575 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1017/S0269727000010575 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bradlow H. Leon The Rockefeller University, 1230 York Avenue, New York, NY10021, U.S.A NATIONALLICENCE 700 1- Michnovicz Jon J. The Rockefeller University, 1230 York Avenue, New York, NY10021, U.S.A NATIONALLICENCE 773 0- Proceedings of the Royal Society of Edinburgh. Section B. Biological Sciences Royal Society of Edinburgh Scotland Foundation 95(1989), 77-86 0269-7270 95<77 1989 95 PRB CC0 http://creativecommons.org/publicdomain/zero/1.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-cambridge