Low oestrogen receptor α expression in normal breast tissue underlies low breast cancer incidence in Japan

Breast cancer incidence and estrogen receptor α in normal mammary tissue—An epidemiologic study among Japanese women in Japan and Hawaii

“…The hypothesis is also supported by the results of several independent investigations that have shown an increase in the level of estrogen receptor ␣ expression as mammary histology progresses from normal to proliferative to carcinoma in situ and eventually invasive carcinoma 6,7 and by a report from a case-control study that the likelihood of breast cancer increases when there is overexpression of estrogen receptors in the normal epithelium. 8,9 Lastly, a role for normal breast tissue estrogen receptor ␣ expression in carcinogenesis is supported by the findings of an earlier investigation 10 showing significantly higher expression of estrogen receptor ␣ in the normal mammary tissue of Caucasian Australian women than in Japanese women in Japan. It may also be of importance that differences in estrogen receptor ␣ expression, in both the study by Lawson and colleagues 10 and the present study, are much more evident among postmenopausal than premenopausal women, in parallel with the higher international variability of breast cancer incidence in the former than in the latter group.…”

“…8,9 Lastly, a role for normal breast tissue estrogen receptor ␣ expression in carcinogenesis is supported by the findings of an earlier investigation 10 showing significantly higher expression of estrogen receptor ␣ in the normal mammary tissue of Caucasian Australian women than in Japanese women in Japan. It may also be of importance that differences in estrogen receptor ␣ expression, in both the study by Lawson and colleagues 10 and the present study, are much more evident among postmenopausal than premenopausal women, in parallel with the higher international variability of breast cancer incidence in the former than in the latter group.…”

“…6 -9 In a recent paper, we have reported that expression of estrogen receptor ␣ is much higher among Australian Caucasian women than among Japanese women in Japan, in parallel with the much higher breast cancer incidence among the former compared with the latter. 10 The incidence of breast cancer among Japanese women in Hawaii is at least twice as high as that among Japanese living in Japan, although not quite as high as the incidence of breast cancer among Caucasians. 5 This is a well-established pattern for migrants from low to high breast cancer risk countries and their descendants.…”

Association of estrogen receptor α polymorphisms with breast cancer risk in older Caucasian women

“…In particular, breast cancer occurs more often when ESR1 is over-expressed in adjacent normal epithelium. 7 Moreover, increased ESR1 expression in normal epithelium is found in older women, 8 as well as in Caucasian women compared to non-Caucasian 9 and Asian 8 women, reflecting age and ethnic-associated patterns of breast cancer risk. In addition, estrogen receptor status is a prognostic factor in breast cancer and a strong predictor of response to endocrine therapy.…”

“…In addition, estrogen receptor status is a prognostic factor in breast cancer and a strong predictor of response to endocrine therapy. 10 The ESR1 gene contains several single nucleotide polymorphisms (SNP) 8,[11][12][13][14] whose functional significance remains unknown. Nonetheless, 2 of these SNP located in intron 1, the IVS1 2401 and IVS1 2354 A/G variants, have been associated with hormonally-related diseases including breast, [15][16][17][18][19] prostate 20 and endometrial 21 cancers.…”