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Oestrogen production rates in blood levels are higher among w American than among Chinese women (Bernstein et al, 1990 higher oestrogen levels have been associated with higher ris breast cancer (Lipworth et al, 1996; Toniolo, 1997). Thus, recent finding (Lipworth et al, 1999) that oestrogens dur pregnancy are higher among Chinese than among white Ame women appears to contradict the hypothesis that pregnancy o gens are positively associated with breast cancer risk in offspring, because the incidence of breast cancer is five t higher among American than among Chinese women. A pos explanation, however, for the apparent contradiction is down-r lation of oestrogen receptor expression during fetal life in resp to higher circulating levels of oestrogens. If this were to be t one should expect lower expression of oestrogen receptors a Chinese women than among American women in respons higher circulating oestrogen levels in the former group. Two lines of evidence suggest that this may, indeed, be the Oestrogen receptor expression in breast cancer tumours is lower among Asian than among Caucasian breast cancer pa (Nomura et al, 1984; Stemmermann, 1991). Moreover, in a s of normal women in the UK, oestrogen receptor expressio normal breast tissue was substantially higher among Euro than among non-European women (Ricketts et al, 1991). S exposure to sex steroids during perinatal life has irrevers effects in experimental animals (Verhoeven et al, 1982), the ex nation for the profound differences in breast cancer incide between Western and Oriental women may be the perma down-regulation of oestrogen receptor expression in fetal hu breast tissues, under the influence of variable levels of pregn oestrogens.

Possible permanent down regulation of oestrogen receptor expression during fetal life and breast cancer risk