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Association of Serum Estrone Levels with Estrogen Receptor-positive Breast Cancer Risk in Postmenopausal Japanese Women¹

Department of Surgical Oncology, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

Purpose: Several reports have demonstrated the association between high serum estrogens levels and breast cancer risk in postmenopausal women. It is hypothesized that breast cancers arising in postmenopausal women with high serum estrogens levels are more likely to be estrogen receptor (ER)-positive. Thus, we have investigated whether or not high serum estrone (E₁) levels are associated with ER-positive breast cancer risk in postmenopausal women.

Experimental Design: A case-control study was conducted on 71 cases (postmenopausal breast cancer patients) and 73 controls (postmenopausal healthy women). Serum E₁ levels were examined in their association with breast cancer risk after adjustment for the various epidemiological risk factors. In addition, clinicopathological characteristics of breast cancers arising in the women with high E₁ levels were investigated.

Results: Women in the high tertile of E₁ levels had a significantly (P < 0.01) increased risk of breast cancer as compared with women in the low tertile [odds ratio (OR), 4.14; 95% confidence interval (CI), 1.44–11.87]. Subset analysis according to the ER status showed that women in the high tertile of E₁ levels had a significantly increased risk for ER-positive breast cancer (OR, 23.79; 95% CI, 3.50–161.59) but not for ER-negative breast cancer (OR, 1.45; 95% CI, 0.41–5.15) as compared with women in the low tertile. Tumor size and lymph node status were not significantly different between women in the high tertile and those in the intermediate and low tertiles. But the frequency of low-histological-grade tumors and ER-positive tumors (88 and 67%, respectively) showed a greater trend toward an increase (P = 0.06 and P = 0.07, respectively) in women in the high tertile than those (69 and 46%, respectively) in the intermediate and low tertiles. In addition, ER levels in ER-positive tumors were significantly (P < 0.05) higher in women in the high tertile (245.3 ± 37.1 fmol/mg protein) than those in the intermediate and low tertiles (134.0 ± 31.3 fmol/mg protein).

Conclusions: Postmenopausal women with high serum E₁ levels have a significantly increased risk for ER-positive, but not ER-negative, breast cancer. Breast cancers arising in women with high E₁ levels show a high ER positivity as well as high ER content. Measurement of serum E₁ levels would be clinically useful in the selection of postmenopausal women who can benefit from prophylactic use of tamoxifen because tamoxifen can prevent ER-positive, but not ER-negative, breast cancer.

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