Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition
Kaaks, R.; Rinaldi, S.; Key, T.J.; Berrino, F.; Peeters, P.H.M.; Biessy, C.; Dossus, L.; Lukanova, A.; Bingham, S.; Khaw, K-T.; Allen, N.E.; Bueno-de-Mesquita, H.B.; Gils, C.H. van; Grobbee, D.E.; Boeing, H.; Lahmann, P.H.; Nagel, G.; Chang-Claude, J.; Clavel-Chapelon, F.; Fournier, A.; Thiébaut, A.; Gonzalez, C.A.; Quirós, J.R.; Tormo, M-J.; Ardanaz, E.; Amiano, P.; Krogh, V.; Palli, D.; Panico, S.; Tumino, R.; Vineis, P.; Trichopoulou, A.; Kalapothaki, V.; Trichopoulos, D.; Ferrari, P.; Norat, T.; Saracci, R.; Riboli, E.
(2005) Endocrine-Related Cancer, volume 12, pp. 1071 - 1082
(Article)
Abstract
Considerable experimental and epidemiological evidence suggests that elevated endogenous sex steroids — notably androgens and oestrogens — promote breast tumour development. In spite of this evidence, postmenopausal androgen replacement therapy with dehydroepiandrosterone (DHEA)
or testosterone has been advocated for the prevention of osteoporosis and improved sexual wellbeing. Wehave conducted a case–control
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study nested within the European Prospective Investigation
into Cancer and Nutrition. Levels of DHEA sulphate (DHEAS), (D4-androstenedione), testosterone, oestrone, oestradiol and sex-hormone binding globulin (SHBG) were measured in prediagnostic serum samples of 677 postmenopausal women who subsequently developed breast cancer and 1309 matched control subjects. Levels of free testosterone and free oestradiol were calculated from absolute concentrations of testosterone, oestradiol and SHBG. Logistic regression models were used to estimate relative risks of breast cancer by quintiles ofhormone concentrations. For all sex steroids – the androgens as well as the oestrogens – elevated serum levels were positively associated with breast cancer risk, while SHBG levels were inversely related to risk. For the androgens, relative risk estimates (95% confidence intervals) between the top and bottom quintiles of the exposure distribution
were:DHEAS1.69 (1.23–2.33), androstenedione 1.94 (1.40–2.69), testosterone 1.85 (1.33–2.57) and
free testosterone 2.50 (1.76–3.55). For the oestrogens, relative risk estimates were: oestrone 2.07
(1.42–3.02), oestradiol 2.28 (1.61–3.23) and free oestradiol (odds ratios 2.13 (1.52–2.98)).
Adjustments for body mass index or other potential confounding factors did not substantially alter
any of these relative risk estimates. Our results have shown that, among postmenopausal women, not
only elevated serum oestrogens but also serum androgens are associated with increased breast
cancer risk. Since DHEAS and androstenedione are largely of adrenal origin in postmenopausal
women, our results indicated that elevated adrenal androgen synthesis is a risk factor for breast
cancer. The results from this study caution against the use of DHEA(S), or other androgens, for postmenopausal androgen replacement therapy.
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Publisher: Society for Endocrinology