Ten years ago we advanced a hypothesis (de Waard et a/., 1964) on the existence of two types of breast cancer with different aetiology. According to this hypothesis, most cases of breast cancer occurring at premenopausal age are connected with an endocrine imbalance in which the ovarian hormones are involved, whereas in the majority of patients with breast cancer occurring after the menopause altered hormonal homeostasis related to overnutrition is the major determinant.Epidemiologic parallelisms between the postmenopausal type of breast cancer and endometrial cancer guided our line of thinking.We had then some evidence from a casecontrol comparison that overweight was more frequent in mammary cancer patients than in the normal population. Moreover, we had found by means of endocrine cytology that among postmenopausal women there was an increased frequency of karyopycnotic (" estrogenic ") smears in those who were obese, hypertensive and diabetic (de Waard and Baanders, 1961 ;de Waard and Oettle, 1965). Since these estrogens originated outside the ovaries (Bruinsma and de Waard, 1959) we felt confident that they were synthetized as such in the adrenal cortex. Subsequently, it was found that only the precursors of extra-ovarian estrogens are synthetized in the adrenal cortex; the conversion of androstenedione to estrogens (mainly estrone) takes place in peripheral tissues ( MacDonald et a/., 1969;Poortman et al., 1973) inter alia in adipose tissue (Schindler et al., 1972).In order to explore possible relationships between nutritional status (in particular obesity), hormonal status (in particular *' adrenal " ceztrogens) and breast-cancer risk in postmenopausal women it was decided to undertake a prospective study.

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